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Type I interferonopathies are a heterogenic group of rare diseases associated with an increase in type I interferon (IFN). The main challenge for the study of Type I interferonopathies is the lack of a well-founded animal model to better characterize the phenotype as well as to perform fast and large drug screenings to offer the best treatment options. In this study, we report the development of a transgenic zebrafish model of Type I interferonopathy overexpressing ifih1 carrying the mutation p.Arg742His (Tg(ifih1_mut)), corresponding to the human mutation p.Arg779His. RNA sequence analysis from Tg(ifih1_mut) larvae revealed a systemic inflammation and IFN signature upon a suboptimal poly I:C induction compared with wild-type larvae, confirming the phenotype observed in patients suffering from Type I interferonopathies. More interestingly, the phenotype was manifested in the zebrafish inflammation and Type I IFN reporters nfkb:eGFP and isg15:eGFP , respectively, making this zebrafish model suitable for future high-throughput chemical screening (HTS). Using the unique advantages of the zebrafish model for gene editing, we have generated Tg(ifih1_mut) knocked down for mavs and ikbke , which completely abrogated the Poly I:C induction and activation of the GFP of the reporters. Finally, we used an FDA-approved drug, Baricitinib (Jak1/Jak2 inhibitor), which was able to reduce the inflammation and the ISG expression. Our results demonstrate the potential of this model to further understand AGS pathological mechanisms and to identify novel therapeutic drugs by HTS. [ABSTRACT FROM AUTHOR]

Novel fertilization strategies, such as the use of biochar-based fertilizers (BBFs) and the co-application of biochar with mineral fertilizers, have shown promising results for mitigating nitrous oxide (N2O) emissions and reducing N losses in agroecosystems. Two greenhouse experiments were performed with radish to evaluate: (1) the mitigation of yield-scaled N2O emissions using BBFs, produced at either 400 or 800 °C and enriched with urea, compared to the co-application of raw biochars with urea; and (2) the N2O mitigation potential of low rates of raw biochars, equivalent to those used with BBFs fertilization, co-applied with low and high N rates (90 and 180 kg N ha−1). BBF produced at 800 °C reduced yield-scaled N2O emissions by 32% as compared to the urea treatment, and by 60%, as compared to the combination of raw biochar with urea. This reduction was attributed to the slow rate of N release in BBF. On the contrary, the co-application of low rates of biochar with urea increased yield-scaled N2O emissions as compared to the fertilization with urea alone. Low rates of biochar (1.4–3.1 t ha−1) reduced yield-scaled N2O emissions only with a high rate of N fertilization. High-pyrolysis-temperature biochar, co-applied with synthetic fertilizer, or used to produce BBFs, demonstrated lower yield-scaled N2O emissions than biochar produced at a lower pyrolysis temperature. This study showed that BBFs are a promising fertilization strategy as compared to the co-application of biochar with synthetic fertilizers. [ABSTRACT FROM AUTHOR]

The interaction of biochar with mineral fertilization has attracted attention as a strategy to reduce N losses and enhance nitrogen use efficiency. In this study, we investigated the coapplication of biochar with two optimized fertilization strategies based on split urea and a microbial inoculant (Azospirillum brasilense) in a commercial pointed white cabbage crop. Additionally, we evaluated a third optimized N fertilization alternative, a biochar‐based fertilizer (BBF) enriched in plant‐available N, which was developed from the same biochar. We assessed environmental impacts such as greenhouse gasses (GHG) and NH3 emissions, yield‐scaled N2O emissions, and global warming potential (GWP). Additionally, we evaluated agronomical outcomes such as crop yield, plant N, and chlorophyll concentration. Moreover, we examined the N‐fixing gene's total and relative abundance (nifH and nifH/16S). Biochar and BBF exhibited similar crop yield, GHG, and NH3 emissions compared to split applications of the synthetic fertilizer. The main difference was associated with the higher soil C sequestration in biochar and BBF treatments that reduced the associated GWP of these fertilization strategies. Finally, biochar favored the activity of the N‐fixing bacteria spread, compared to the sole application of bacteria and BBF demonstrated a promoting effect in the soil's total abundance of natural N‐fixing bacteria. [ABSTRACT FROM AUTHOR]

The agronomic use of compost and biochar as soil amendments may exhibit contrasting results in terms of soil fertility and plant nutrition. The effects of the biennial application of biochar, compost and a blend of compost:biochar (90:10; % dw:dw) on the agronomical performance of an organically managed and well established 25-year-old olive orchard was assessed 5 years after the initial application. The agronomical evaluation was based on the assessment of the soil physical, chemical, and biological characteristics, and the assessment of the soil fertility by both crop production and nutritional status of the orchard, and the bioassay with olive plantlets. Biochar mainly benefited the physical properties (bulk density, total porosity, aeration, water retention capacity) of soil, especially in the top 0–5 cm. Compost and its blend with biochar improved microbial activity, soil nutritional status (increasing the content of soluble organic C, N, and P) and favoured the formation of aggregates in soil. The bioassay conducted with young plantlets confirmed the enhanced soil fertility status in the three amended treatments, particularly in the case of biochar and its blend with compost. However, this effect was not significantly observed in the adult plants after 5 years of application, reflecting the slow response of adult olive trees to changes in fertilization. Based on these results, alongside the desirable long-residence time of biochar in soil and the ready availability of compost, the blend of biochar with compost assayed in this study is defined as a valid strategy for preparing high quality soil organic amendments. [ABSTRACT FROM AUTHOR]

Introduction: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), manifests as persistent and often debilitating symptoms enduring well beyond the initial COVID-19 infection. This disease is especially worrying in children since it can seriously alter their development. Presently, a specific diagnostic test or definitive biomarker set for confirming long COVID is lacking, relying instead on the protracted presence of symptoms postacute infection. Methods: We measured the levels of 13 biomarkers in 105 saliva samples (49 from children with long COVID and 56 controls), and the Pearson correlation coefficient was used to analyse the correlations between the levels of the different salivary biomarkers. Multivariate logistic regression analyses were performed to determine which of the 13 analysed salivary biomarkers were useful to discriminate between children with long COVID and controls, as well as between children with mild and severe long COVID symptoms. Results: Pediatric long COVID exhibited increased oxidant biomarkers and decreased antioxidant, immune response, and stress-related biomarkers. Correlation analyses unveiled distinct patterns between biomarkers in long COVID and controls. Notably, a multivariate logistic regression pinpointed TOS, ADA2, total proteins, and AOPP as pivotal variables, culminating in a remarkably accurate predictive model distinguishing long COVID from controls. Furthermore, total proteins and ADA1 were instrumental in discerning between mild and severe long COVID symptoms. Discussion: This research sheds light on the potential clinical utility of salivary biomarkers in diagnosing and categorizing the severity of pediatric long COVID. It also lays the groundwork for future investigations aimed at unravelling the prognostic value of these biomarkers in predicting the trajectory of long COVID in affected individuals. [ABSTRACT FROM AUTHOR]

Zebrafish are an emergent animal model to study human diseases due to their significant genetic similarity to humans, swift development, and genetic manipulability. Their utility extends to the exploration of the involvement of inflammation in host defense, immune responses, and tissue regeneration. Additionally, the zebrafish model system facilitates prompt screening of chemical compounds that affect inflammation. This study explored the diverse roles of inflammatory pathways in zebrafish development and aging. Serving as a crucial model, zebrafish provides insights into the intricate interplay of inflammation in both developmental and aging contexts. The evidence presented suggests that the same inflammatory signaling pathways often play instructive or beneficial roles during embryogenesis and are associated with malignancies in adults. [ABSTRACT FROM AUTHOR]

This correction notice from Frontiers in Immunology addresses an error in the funding statement of an article on a zebrafish model of Aicardi-Goutières syndrome. The correct funding sources are Instituto de Salud Carlos III, Consejería de Salud de la Región de Murcia, Spanish Ministry of Science and Innovation, and the European Union. The authors acknowledge the mistake but clarify that it does not impact the scientific conclusions of the study. [Extracted from the article]

Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to increase knowledge and develop new targeted therapies. We have recently demonstrated the critical role of NAD+ and poly (ADP-ribose) (PAR) metabolism in oxidative stress and skin inflammation. Specifically, we found that hyperactivation of PARP1 in response to DNA damage induced by reactive oxygen species, and fueled by NAMPT-derived NAD+, mediated inflammation through parthanatos cell death in zebrafish and human organotypic 3D skin models of psoriasis. Furthermore, the aberrant induction of NAMPT and PARP activity was observed in the lesional skin of psoriasis patients, supporting the role of these signaling pathways in psoriasis and pointing to NAMPT and PARP1 as potential novel therapeutic targets in treating skin inflammatory disorders. In the present work, we report, for the first time, altered NAD+ and PAR metabolism in the skin of AD patients and a strong correlation between NAMPT and PARP1 expression and the lesional status of AD. Furthermore, using a human 3D organotypic skin model of AD, we demonstrate that the pharmacological inhibition of NAMPT and PARP reduces pathology-associated biomarkers. These results help to understand the complexity of AD and reveal new potential treatments for AD patients. [ABSTRACT FROM AUTHOR]

Several studies have revealed a correlation between chronic inflammation and nicotinamide adenine dinucleotide (NAD+) metabolism, but the precise mechanism involved is unknown. Here, we report that the genetic and pharmacological inhibition of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in the salvage pathway of NAD+ biosynthesis, reduced oxidative stress, inflammation, and keratinocyte DNA damage, hyperproliferation, and cell death in zebrafish models of chronic skin inflammation, while all these effects were reversed by NAD+ supplementation. Similarly, genetic and pharmacological inhibition of poly(ADP-ribose) (PAR) polymerase 1 (Parp1), overexpression of PAR glycohydrolase, inhibition of apoptosis-inducing factor 1, inhibition of NADPH oxidases, and reactive oxygen species (ROS) scavenging all phenocopied the effects of Nampt inhibition. Pharmacological inhibition of NADPH oxidases/NAMPT/PARP/AIFM1 axis decreased the expression of pathology-associated genes in human organotypic 3D skin models of psoriasis. Consistently, an aberrant induction of NAMPT and PARP activity, together with AIFM1 nuclear translocation, was observed in lesional skin from psoriasis patients. In conclusion, hyperactivation of PARP1 in response to ROS-induced DNA damage, fueled by NAMPT-derived NAD+, mediates skin inflammation through parthanatos cell death. A study of chronic skin inflammation reveals that hyperactivation of PARP1 in response to ROS-induced DNA damage, fueled by NAMPT-derived NAD+, mediates skin inflammation via parthanatos cell death, identifying NAMPT, PARP1 and AIFM1 as novel therapeutic targets for psoriasis. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Agronomic uses of biochar have been intensely explored in the last 15 years. Recently, a new generation of biochar‐based fertilizers has been developed. Raw biochar (BCH), nitrogen‐enriched biochar (N + BCH) or urea were added to a coir fiber‐based substrate for tomato cultivation, to assess seed germination, growth and fruiting of two cultivars (Cuarenteno and Moneymaker).BCH stimulated seed germination and early radicle growth, possibly because of the presence of karrikins detected in both BCH and N‐BCH (0.039 and 0.044 mg kg−1, respectively). However, BCH reduced growth in adult plants in both cultivars, probably because of ammonium retention, causing low‐N‐stress‐related symptoms such as accumulation of flavonoids in the leaf. Urea was toxic for seed germination because of the fast release of ammonium, but caused a positive effect on adult plant growth and yield, increasing chlorophyll in both cultivars, quantum yield and ascorbic acid in cv. Cuarenteno, and decreasing flavonoids and peroxide in leaves of both cultivars. Unlike urea, N + BCH showed a positive impact on plant growth and yield, but without releasing high amounts of ammonium or negatively affecting seed germination. Nitrogen‐rich amendments reduced phosphorus and increased iron leaf content in both cultivars.BCH can be effectively used as a growth medium constituent in nurseries for seedling production, whereas N + BCH offers a promising alternative to urea or other nitrogen mineral fertilizers for crop cultivation. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]