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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.

Abstract Background The release of organic acids (OAs) is considered the main mechanism used by phosphate-solubilizing bacteria (PSB) to dissolve inorganic phosphate in soil. Nevertheless, little is known about the effect of individual OAs produced by a particular PSB in a soil–plant system. For these reasons, the present work aimed at investigating the effect of Enterobacter sp. strain 15S and the exogenous application of its OAs on (i) the solubilization of tricalcium phosphate (TCP), (ii) plant growth and (iii) P nutrition of cucumber. To this purpose two independent experiments have been performed. Results In the first experiment, carried out in vitro, the phosphate solubilizing activity of Enterobacter 15S was associated with the release of citric, fumaric, ketoglutaric, malic, and oxalic acids. In the second experiment, cucumber plants were grown in a Leonard jar system consisting of a nutrient solution supplemented with the OAs previously identified in Enterobacter 15S (jar’s base) and a substrate supplemented with the insoluble TCP where cucumber plants were grown (jar’s top). The use of Enterobacter 15S and its secreted OAs proved to be efficient in the in situ TCP solubilization. In particular, the enhancement of the morpho-physiological traits of P-starved cucumber plants was evident when treated with Enterobacter 15S, oxalate, or citrate. The highest accumulation of P in roots and shoots induced by such treatments further corroborated this hypothesis. Conclusion In our study, the results presented suggest that organic acids released by Enterobacter 15S as well as the bacterium itself can enhance the P-acquisition by cucumber plants.

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.

A field trial was carried out to investigate the effects of compost application on a young Cabernet sauvignon vineyard located in a hilly area in the North-East of Italy and subjected to land terracing before plantation. The use of a compost based on manure, pruning residues and pomace at a rate of 65 t ha-1 was compared to the mineral fertilization regime recommended for the vineyards in the area (NPK: 80, 50, 200 kg ha-1). A multi-factorial approach that considered soil chemical properties, microbial community structure and function, vine nutritional and vegetative indexes, yield and quality parameters was applied in the attempt of depict interrelated effects of compost on all these factors. Results of this study show that the application of compost for three consequent years greatly increased soil organic matter content and improved the mineral nutrient availability in the soil. Soil biological fertility showed a slow but significant response to compost addition as from the second year of treatment microbial growth and enzyme activity were increased compared to those of the inorganic fertilization, with special regard to enzymes involved in P cycle. A shift in the soil microbial community structure was also observed in compost-treated soil, with higher presence of copiotrophic bacteria, indicators of soil quality, and phosphorus solubilizing bacteria. A decrease of pathogenic fungal strains was also observed. Organic fertilization increased plant nutrient uptake and vegetative growth compared to those observed in chemically fertilized vines. A trend toward increased yield and improvements for some grape quality parameters such as acidity and pH were observed in the first year of production. These results provide evidence that compost can boost soil fertility restoration in vineyard disturbed by land terracing, allowing for agronomic performances comparable or even improved than those of chemically fertilized vines.

The present paper focuses on the shear strength exhibited by rocks and soils when sliding along dry and wet surfaces, with this mechanism of failure being strongly related to the water lubrication phenomenon. It is well known that the frictional behaviour of geomaterials requires multiscale investigation. Under this perspective, experimental evidence of both friction at the grain scale (i.e. interparticle friction) and friction along sliding surfaces of rock and granular soil samples (i.e. surface friction) are analysed by using data from the literature. The review is addressed at linking different scales, stating the differences between rocks and soils in terms of frictional response to sliding and trying to point out still open problems for the research.

Summary: Acidic environments reduce the intracellular pH (pHi) of most cells to levels that are sub-optimal for growth and cellular functions. Yet, cancers maintain an alkaline cytoplasm despite low extracellular pH (pHe). Raised pHi is thought to be beneficial for tumor progression and invasiveness. However, the transport mechanisms underpinning this adaptation have not been studied systematically. Here, we characterize the pHe-pHi relationship in 66 colorectal cancer cell lines and identify the acid-loading anion exchanger 2 (AE2, SLC4A2) as a regulator of resting pHi. Cells adapt to chronic extracellular acidosis by degrading AE2 protein, which raises pHi and reduces acid sensitivity of growth. Acidity inhibits mTOR signaling, which stimulates lysosomal function and AE2 degradation, a process reversed by bafilomycin A1. We identify AE2 degradation as a mechanism for maintaining a conducive pHi in tumors. As an adaptive mechanism, inhibiting lysosomal degradation of AE2 is a potential therapeutic target.

Urban Heat Islands (UHI) phenomenon is a pressing problem for highly industrialized areas with serious risks for public health. Weather stations guarantee long-term accurate observations of weather parameters, such Air Temperature (AT), but lack appropriate spatial coverage. Numerous studies have argued that satellite Land Surface Temperature (LST) is a relevant parameter for estimating AT maps, exploring both linear regression and Machine Learning algorithms. This study proposes a Neural Network (NN) regression model for estimating the maximum AT from Landsat-8 data. The approach has been tested in a variegated morphological region (Puglia, Italy) using a large stack of data acquired from 2018 to 2020. The algorithm uses the median values of LST and Normalized Difference Vegetation Index (NDVI) computed using different buffer radius around the location of each reference weather station (250 m, 1000 m, and 2000 m) to train the NN model with a K-fold cross-validation strategy. The reference dataset was split into three sets using a stratified sampling approach considering the different station categories: rural, High- and Low-density Urban areas respectively. The algorithm was tested with different learning rates (LR) (0.001 and 0.005). The results show that our NN model accuracy improves with the increase of the buffer radius, minimizing the difference in terms of R^2 between training and evaluation data, with an overall accuracy consistently higher than 0.84. Future research could investigate more input variables in the NN model such as morphology or climate variables and test the algorithm on larger areas.

Plants have evolved diverse plant-species specific tolerance mechanisms to cope with salt stress. However, these adaptive strategies often inefficiently mitigate the stress related to increasing salinity. In this respect, plant-based biostimulants have gained increasing popularity since they can alleviate deleterious effects of salinity. Hence, this study aimed to evaluate the sensitivity of tomato and lettuce plants grown under high salinity and the possible protective effects of four biostimulants based on vegetal protein hydrolysates. Plants were set in a 2 × 5 factorial experimental design completely randomized with two salt conditions, no salt (0 mM) and high salt (120 mM for tomato or 80 mM for lettuce), and five biostimulant treatments (C: Malvaceae-derived, P: Poaceae-derived, D: Legume-derived commercial ‘Trainer®’, H: Legume-derived commercial ‘Vegamin®’, and Control: distilled water). Our results showed that both salinity and biostimulant treatments affected the biomass accumulation in the two plant species, albeit to different extents. The salinity stress induced a higher activity of antioxidant enzymes (e.g., catalase, ascorbate peroxidase, guaiacol peroxidase and superoxide dismutase) and the overaccumulation of osmolyte proline in both lettuce and tomato plants. Interestingly, salt-stressed lettuce plants showed a higher accumulation of proline as compared to tomato plants. On the other hand, the treatment with biostimulants in salt-stressed plants caused a differential induction of enzymatic activity depending on the plant and the biostimulant considered. Overall, our results suggest that tomato plants were constitutively more tolerant to salinity than lettuce plants. As a consequence, the effectiveness of biostimulants in alleviating high salt concentrations was more evident in lettuce. Among the four biostimulants tested, P and D showed to be the most promising for the amelioration of salt stress in both the plant species, thereby suggesting their possible application in the agricultural practice.

Introducción: Streptococcus pneumoniae (Spn) ocasionalmente causa infección intraabdominal (IIASpn) que puede ser: 1) peritonitis bacteriana espontánea (PBE) en paciente añosos con enfermedad peritoneal previa, asociada con cirrosis, en la mayoría de los casos; 2) asociada o adyacente a un órgano intraabdominal o postquirúrgica (IIAbq); 3) peritonitis en mujeres jóvenes previamente sanas (MJPS). Nuestro objetivo es reportar 18 casos de IIASpn describiendo: presentación clínica, comorbilidades, necesidad de cirugía, microbiología y sensibilidad a los antimicrobianos, conducta terapéutica y evolución. Métodos: estudio de 18 pacientes adultos con IIASpn en un período de 23 años. Análisis de las características clínicas, microbiología y evolución de los pacientes. Resultados: las IIASpn ocurrieron en 9 MJPS, 6 varones y una mujer con PBE, y 2 varones con apendicitis. Las MJPS fueron intervenidas quirúrgicamente (4 pelviperitonitis, 3 salpingitis y 2 abscesos tubo ovárico) y evolucionaron favorablemente. En las muestras intraoperatorias se aisló Spn cultivo puro sensible a penicilina. Tres de cuatro pacientes tuvieron hemocultivo positivo. Cinco de siete pacientes con PBE fallecieron y en las muestras de líquido peritoneal desarrolló Spn cultivo puro. Gran porcentaje de cepas presentó sensibilidad disminuida a penicilina. Cuatro de cinco, tuvieron hemocultivo positivo. Los pacientes con apendicitis evolucionaron favorablemente. Conclusiones: La IIASpn en MJPS fue la presentación más frecuente, la cirugía jugó un rol significativo en el tratamiento y la respuesta clínica fue excelente. La segunda presentación ocurrió en pacientes añosos con cirrosis y en su mayoría, fallecieron. La apendicitis fue la tercera presentación en pacientes que evolucionaron favorablemente.

Growth of cancer cells in vitro can be attenuated by genetically inactivating selected metabolic pathways. However, loss-of-function mutations in metabolic pathways are not negatively selected in human cancers, indicating that these genes are not essential in vivo. We hypothesize that spontaneous mutations in ‘metabolic genes’ will not necessarily produce functional defects because mutation-bearing cells may be rescued by metabolite exchange with neighboring wild-type cells via gap junctions. Using fluorescent substances to probe intercellular diffusion, we show that colorectal cancer (CRC) cells are coupled by gap junctions assembled from connexins, particularly Cx26. Cells with genetically inactivated components of pH regulation (SLC9A1), glycolysis (ALDOA), or mitochondrial respiration (NDUFS1) could be rescued through access to functional proteins in co-cultured wild-type cells. The effect of diffusive coupling was also observed in co-culture xenografts. Rescue was largely dependent on solute exchange via Cx26 channels, a uniformly and constitutively expressed isoform in CRCs. Due to diffusive coupling, the emergent phenotype is less heterogenous than its genotype, and thus an individual cell should not be considered as the unit under selection, at least for metabolite-handling processes. Our findings can explain why certain loss-of-function mutations in genes ascribed as ‘essential’ do not influence the growth of human cancers.

Summary: Unlike most cell types, many cancer cells survive at low extracellular pH (pHe), a chemical signature of tumors. Genes that facilitate survival under acid stress are therefore potential targets for cancer therapies. We performed a genome-wide CRISPR-Cas9 cell viability screen at physiological and acidic conditions to systematically identify gene knockouts associated with pH-related fitness defects in colorectal cancer cells. Knockouts of genes involved in oxidative phosphorylation (NDUFS1) and iron-sulfur cluster biogenesis (IBA57, NFU1) grew well at physiological pHe, but underwent profound cell death under acidic conditions. We identified several small-molecule inhibitors of mitochondrial metabolism that can kill cancer cells at low pHe only. Xenografts established from NDUFS1−/− cells grew considerably slower than their wild-type controls, but growth could be stimulated with systemic bicarbonate therapy that lessens the tumoral acid stress. These findings raise the possibility of therapeutically targeting mitochondrial metabolism in combination with acid stress as a cancer treatment option.

Food authenticity plays a pivotal role in the modern age since an increased consumers awareness has led them to pay more attention to food commodities. For this reason, it is important to have reliable and fast techniques able to detect possible adulterations in food, which affect qualitative and economic value. Therefore, the aim of this study was to detect possible adulterations in apple juice from others fruit species (i.e., pear, peach, and kiwi) combining DNA barcoding approach, using trnL (UAA) intron, with high resolution melting analysis (HRMA). A preliminary phylogenetic analysis, using sequences retrieved by the GenBank, confirmed the discriminatory power of trnL (UAA) intron among the four fruit species examined. Moreover, the sequencing of the trnL (UAA) fragments obtained from apple, pear, peach, and kiwi, demonstrated the suitability of an inner shorter sequence, P6 loop, to differentiate the considered species. The HRMA coupled with trnL (UAA) intron allowed discrimination among the four fruits but provided incomplete results for juices. Whereas the HRMA targeting the P6 loop amplicons confirmed the suitability of the technique to qualitatively distinguish fruit juices composed by the combination of apple/pear and apple/peach. However, the impossibility of discriminating apple/kiwi juices from the pure kiwi sample highlighted limitations, most likely related to the DNA extraction process. This hypothesis was further confirmed by analyzing DNA blends obtained by combining nucleic acids extracted from pure matrixes (i.e., apple and kiwi fruits). In this specific case, the application of HRMA allowed both qualitative and quantitative assessment of the samples.

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]

Introducción: Aeromonas es una causa habitual de gastroenteritis pero ocasionalmente puede producir infecciones extraintestinales. La incidencia de bacteriemia por este género es muy baja y en general los pacientes presentan enfermedades de base asociadas. Materiales y métodos: Análisis retrospectivo de los episodios de bacteriemias por Aeromonas spp. durante un período de ocho años en el Hospital Nacional de Clínicas de la ciudad de Córdoba, haciendo hincapié en edad, sexo, comorbilidades asociadas, presentación clínica, foco, origen de la infección, evolución clínica, prevalencia de especies y sensibilidad antimicrobiana de las mismas. Resultados: Se registraron 10 episodios de bacteriemias por Aeromonas spp. El 60% correspondieron a mujeres y el 40% a hombres. La edad promedio fue 65 años. En siete pacientes el origen de la infección fue comunitario y en tres nosocomial. El 70% de los pacientes presentaron patologías de base predisponentes. El foco de la bacteriemia fue abdominal en dos casos. A. complejo hydrophila fue responsable del 50% de los casos. El 80% de las bacteriemias fueron monomicrobianas. Los aislamientos generalmente presentaron altos porcentajes de sensibilidad. Conclusión: Las bacteriemias se presentaron en pacientes de ambos sexos, de edad avanzada, la mayoría de los cuales poseían comorbilidades asociadas. La mayoría de las infecciones tuvieron su origen en la comunidad. Si bien la bacteriemia por Aeromonas spp. es poco frecuente, la mortalidad encontrada en nuestro estudio fue relativamente elevada a pesar del alto porcentaje de sensibilidad a los antimicrobianos.

ResumenIntroducción: Streptococcus agalactiae (SGB) es un reconocido patógeno asociado a infecciones en recién nacidos y lactantes pequeños, en mujeres gestantes y en puérperas. En los últimos años se ha observado un incremento de infecciones por este agente en pacientes adultos no gestantes, siendo más frecuentes en mayores de 65 años y con alguna comorbilidad.Métodos: estudio retrospectivo y observacional de muestras de pacientes adultos no gestantes analizadas en el laboratorio de Bacteriología del Hospital Nacional de Clínicas de la ciudad de Córdoba, desde enero de 2008 a diciembre de 2017. Se analizó edad y sexo de los pacientes, comorbilidades y tipo de muestra.Resultados: El total de muestras positivas fue de 187, 91 (49%) correspondieron a mujeres y 96 (51%) a varones. La edad media fue de 67 años. De las muestras, orina fue la prevalente con 90 aislamientos (48.1%), seguidas de sangre con 39 (20.8%) y piel y partes blandas con 38 (20.3%). De los 187 adultos, 177 (95%) presentaron al menos una comorbilidad, siendo la más frecuente diabetes, seguida de neoplasias. Sólo 10 (5%) no presentaron comorbilidades.Conclusión: Los hallazgos en nuestro trabajo, como así también los publicados por diversos autores, ponen en evidencia la necesidad de considerar a Streptococcus agalactiae no sólo un patógeno de neonatos y embarazadas, sino también de pacientes adultos mayores y con diferentes comorbilidades, en especial aquellos que padecen DBT o neoplasias.Palabras claves: Streptococcus agalactiae; infecciones estreptocócicas; inmunosupresión; bacteriemia; comorbilidad

Abstract Background Positron emission tomography (PET) using translocator protein (TSPO) ligands has been used to detect neuroinflammatory processes in neurological disorders, including multiple sclerosis (MS). The aim of this study was to evaluate neuroinflammation in a mouse MS model (EAE) using TSPO-PET with 18F-VC701, in combination with magnetic resonance imaging (MRI). Methods MOG35-55/CFA and pertussis toxin protocol was used to induce EAE in C57BL/6 mice. Disease progression was monitored daily, whereas MRI evaluation was performed at 1, 2, and 4 weeks post-induction. Microglia activation was assessed in vivo by 18F-VC701 PET at the time of maximum disease score and validated by radioligand ex vivo distribution and immunohistochemistry at 2 and 4 weeks post-immunization. Results In vivo and ex vivo analyses show that 18F-VC701 significantly accumulates within the central nervous system (CNS), particularly in the cortex, striatum, hippocampus, cerebellum, and cervical spinal cord of EAE compared to control mice, at 2 weeks post-immunization. MRI confirmed the presence of focal brain lesions at 2 weeks post-immunization in both T1-weighted and T2 images. Of note, MRI abnormalities attenuated in later post-immunization phase. Neuropathological analysis confirmed the presence of microglial activation in EAE mice, consistent with the in vivo increase of 18F-VC701 uptake. Conclusion Increase of 18F-VC701 uptake in EAE mice is strongly associated with the presence of microglia activation in the acute phase of the disease. The combined use of TSPO-PET and MRI provided complementary evidence on the ongoing disease process, thus representing an attractive new tool to investigate neuronal damage and neuroinflammation at preclinical levels.