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Iron (Fe) deficiency in crops significantly reduces yield, impacting agricultural productivity worldwide. Synthetic Fe chelates are commonly applied as fertilizers to address this issue, but their synthetic nature and prolonged use poses environmental risks. Thus, inoculation of plant growth-promoting bacteria rises as an alternative to enhance Fe uptake in crops while minimizing reliance on synthetic chelates. This study aimed to examine the influence of Pseudomonas RMC4 inoculation and pyoverdine application on cucumber plants cultivated hydroponically under Fe deficiency conditions. Evaluations included the SPAD index, plant biomass, root morphology, Fe-chelate reductase activity, gene expression, and ionomic analysis. Following Fe deficiency, Pseudomonas RMC4 inoculation improved the SPAD index, increased dry weight, enhanced root development, and facilitated Fe acquisition mechanisms, thus, fostering the endogenous resilience of the plant to the limited Fe availability. This improvement was observed with bacterial inoculation or pyoverdine application alongside an insoluble Fe source (ferrihydrite). Overall, the results suggest the beneficial impact of Pseudomonas RMC4 inoculation in alleviating symptoms of Fe deficiency. Future studies will investigate bacterial application under field conditions to assess its potential in replacing synthetic Fe-chelates fertilizers in crop production in favor of more sustainable agriculture.

Abstract Plant biostimulants are widely applied in agriculture for their ability to improve plant fitness. In the present work, the impact of Graminaceae-derived protein hydrolysate (P) and its lighter molecular fraction F3 (

Abstract Plasma-derived therapeutic proteins are produced through an industrial fractionation process where proteins are purified from individual intermediates, some of which remain unused and are discarded. Relatively few plasma-derived proteins are exploited clinically, with most of available plasma being directed towards the manufacture of immunoglobulin and albumin. Although the plasma proteome provides opportunities to develop novel protein replacement therapies, particularly for rare diseases, the high cost of plasma together with small patient populations impact negatively on the development of plasma-derived orphan drugs. Enabling therapeutics development from unused plasma fractionation intermediates would therefore constitute a substantial innovation. To this objective, we characterized the proteome of unused plasma fractionation intermediates and prioritized proteins for their potential as new candidate therapies for human disease. We selected ceruloplasmin, a plasma ferroxidase, as a potential therapy for aceruloplasminemia, an adult-onset ultra-rare neurological disease caused by iron accumulation as a result of ceruloplasmin mutations. Intraperitoneally administered ceruloplasmin, purified from an unused plasma fractionation intermediate, was able to prevent neurological, hepatic and hematological phenotypes in ceruloplasmin-deficient mice. These data demonstrate the feasibility of transforming industrial waste plasma fraction into a raw material for manufacturing of new candidate proteins for replacement therapies, optimizing plasma use and reducing waste generation.

Summary: Malignancy is enabled by pro-growth mutations and adequate energy provision. However, global metabolic activation would be self-terminating if it depleted tumor resources. Cancer cells could avoid this by rationing resources, e.g., dynamically switching between “baseline” and “activated” metabolic states. Using single-cell metabolic phenotyping of pancreatic ductal adenocarcinoma cells, we identify MIA-PaCa-2 as having broad heterogeneity of fermentative metabolism. Sorting by a readout of lactic acid permeability separates cells by fermentative and respiratory rates. Contrasting phenotypes persist for 4 days and are unrelated to cell cycling or glycolytic/respiratory gene expression; however, transcriptomics links metabolically active cells with interleukin-6 receptor (IL-6R)-STAT3 signaling. We verify this by IL-6R/STAT3 knockdowns and sorting by IL-6R status. IL-6R/STAT3 activates fermentation and transcription of its inhibitor, SOCS3, resulting in delayed negative feedback that underpins transitions between metabolic states. Among cells manifesting wide metabolic heterogeneity, dynamic IL-6R/STAT3 signaling may allow cell cohorts to take turns in progressing energy-intense processes without depleting shared resources.

The application of protein hydrolysates (PH) biostimulants is considered a promising approach to promote crop growth and resilience against abiotic stresses. Nevertheless, PHs bioactivity depends on both the raw material used for their preparation and the molecular fraction applied. The present research aimed at investigating the molecular mechanisms triggered by applying a PH and its fractions on plants subjected to nitrogen limitations. To this objective, an integrated transcriptomic‐metabolomic approach was used to assess lettuce plants grown under different nitrogen levels and treated with either the commercial PH Vegamin® or its molecular fractions PH1(>10 kDa), PH2 (1–10 kDa) and PH3 (<1 kDa). Regardless of nitrogen provision, biostimulant application enhanced lettuce biomass, likely through a hormone‐like activity. This was confirmed by the modulation of genes involved in auxin and cytokinin synthesis, mirrored by an increase in the metabolic levels of these hormones. Consistently, PH and PH3 upregulated genes involved in cell wall growth and plasticity. Furthermore, the accumulation of specific metabolites suggested the activation of a multifaceted antioxidant machinery. Notwithstanding, the modulation of stress‐response transcription factors and genes involved in detoxification processes was observed. The coordinated action of these molecular entities might underpin the increased resilience of lettuce plants against nitrogen‐limiting conditions. In conclusion, integrating omics techniques allowed the elucidation of mechanistic aspects underlying PH bioactivity in crops. Most importantly, the comparison of PH with its fraction PH3 showed that, except for a few peculiarities, the effects induced were equivalent, suggesting that the highest bioactivity was ascribable to the lightest molecular fraction. [ABSTRACT FROM AUTHOR]