Influence of Metal Salts Addition on Physical and Electrochemical Properties of Ethyl and Propylammonium Nitrate

In this work, we deepen in the characterization of two protic ionic liquids (PILs), ethylammonium nitrate (EAN) and propylammonium nitrate (PAN). With this aim, we determined the influence of inorganic nitrate salts addition on their physical properties and their electrochemical potential window (EPW). Thus, experimental measurements of electrical conductivity, density, viscosity, refractive index and surface tension of mixtures of {EAN or PAN + LiNO₃, Ca(NO₃)₂, Mg(NO₃)₂ or Al(NO₃)₃} at a temperature range between 5 and 95 °C are presented first, except for the last two properties which were measured at 25 °C. In the second part, the corresponding EPWs were determined at 25 °C by linear sweep voltammetry using three different electrochemical cells. Effect of the salt addition was associated mainly with the metal cation characteristics, so, generally, LiNO₃ showed the lower influence, followed by Ca(NO₃)₂, Mg(NO₃)₂ or Al(NO₃)₃. The results obtained for the EAN + LiNO₃ mixtures, along with those from a previous work, allowed us to develop novel predictive equations for most of the presented physical properties as functions of the lithium salt concentration, the temperature and the water content. Electrochemical results showed that a general order of EPW can be established for both PILs, although exceptions related to measurement conditions and the properties of the mixtures were found.     

Poly(dithiophosphate)s,a New Class of Phosphorus- and Sulfur-Containing Functional Polymers by a Catalyst-Free Facile Reaction between Diols and Phosphorus Pentasulfide

Novel poly(dithiophosphate)s (PDTPs) were successfully synthesized under mild conditions without any additive in the presence of THF or toluene diluents at 60 °C by a direct, catalyst-free reaction between the abundant phosphorus pentasulfide (P₄S₁₀) and glycols such as ethylene glycol (EG), 1,6-hexanediol (HD) and poly(ethylene glycol) (PEG). GPC, FTIR, ¹H and ³¹P NMR analyses proved the formation of macromolecules with dithiophosphate coupling groups having P=S and P-SH pendant functionalities. Surprisingly, the ring-opening of THF by the P-SH group and its pendant incorporation as a branching point occur during polymerization. This process is absent with toluene, providing conditions to obtain linear chains. ³¹P NMR measurements indicate long-time partial hydrolysis and esterification, resulting in the formation of a thiophosphoric acid moiety and branching points. Copolymerization, i.e., using mixtures of EG or HD with PEG, results in polymers with broadly varying viscoelastic properties. TGA shows the lower thermal stability of PDTPs than that of PEG due to the relatively low thermal stability of the P-O-C moieties. The low T_gs of these polymers, from −4 to −50 °C, and a lack of PEG crystallites were found by DSC. This polymerization process and the resulting novel PDTPs enable various new routes for polymer synthesis and application possibilities.     

Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats

Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular tissue memory that may be transmitted through soluble signaling messengers, transferred from humans to healthy recipient animals, and consequently drive the recapitulation of arterial wall thickening and other vascular pathologies. We examined the effects of the intralesional infiltration for 6 days of arteriosclerotic popliteal artery-derived homogenates (100 µg of protein) into rats’ full-thickness wounds granulation tissue. Animals infiltrated with normal saline solution or healthy brachial arterial tissue homogenate obtained from traumatic amputation served as controls. The significant thickening of arteriolar walls was the constant outcome in two independent experiments for animals receiving arteriosclerotic tissue homogenates. This material induced other vascular morphological changes including an endothelial cell phenotypic reprogramming that mirrored the donor’s vascular histopathology. The immunohistochemical expression pattern of relevant vascular markers appeared to match between the human tissue and the corresponding recipient rats. These changes occurred within days of administration, and with no cross-species limitation. The identification of these “vascular disease drivers” may pave novel research avenues for atherosclerosis pathobiology.     

Deciphering the Complex Molecular Pathogenesis of Myotonic Dystrophy Type 1 through Omics Studies

Omics studies are crucial to improve our understanding of myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults. Employing tissue samples and cell lines derived from patients and animal models, omics approaches have revealed the myriad alterations in gene and microRNA expression, alternative splicing, 3′ polyadenylation, CpG methylation, and proteins levels, among others, that contribute to this complex multisystem disease. In addition, omics characterization of drug candidate treatment experiments provides crucial insight into the degree of therapeutic rescue and off-target effects that can be achieved. Finally, several innovative technologies such as single-cell sequencing and artificial intelligence will have a significant impact on future DM1 research.     

Gal3 Plays a Deleterious Role in a Mouse Model of Endotoxemia

Lipopolysaccharide (LPS)-induced endotoxemia induces an acute systemic inflammatory response that mimics some important features of sepsis, the disease with the highest mortality rate worldwide. In this work, we have analyzed a murine model of endotoxemia based on a single intraperitoneal injection of 5 mg/kg of LPS. We took advantage of galectin-3 (Gal3) knockout mice and found that the absence of Gal3 decreased the mortality rate oflethal endotoxemia in the first 80 h after the administration of LPS, along with a reduction in the tissular damage in several organs measured by electron microscopy. Using flow cytometry, we demonstrated that, in control conditions, peripheral immune cells, especially monocytes, exhibited high levels of Gal3, which were early depleted in response to LPS injection, thus suggesting Gal3 release under endotoxemia conditions. However, serum levels of Gal3 early decreased in response to LPS challenge (1 h), an indication that Gal3 may be extravasated to peripheral organs. Indeed, analysis of Gal3 in peripheral organs revealed a robust up-regulation of Gal3 36 h after LPS injection. Taken together, these results demonstrate the important role that Gal3 could play in the development of systemic inflammation, a well-established feature of sepsis, thus opening new and promising therapeutic options for these harmful conditions.     

Short-Term Immune Responses of Gilthead Seabream (Sparus aurata) Juveniles against Photobacterium damselae subsp. piscicida

Photobacteriosis is a septicaemic bacterial disease affecting several marine species around the globe, resulting in significant economic losses. Although many studies have been performed related to the pathogen virulence and resistance factors, information regarding the host defence mechanisms activated once an infection takes place is still scarce. The present study was designed to understand innate immune responses of farmed juvenile gilthead seabream (Sparus aurata) after Photobacterium damselae subsp. piscicida (Phdp) infection. Therefore, two groups of seabream juveniles were intraperitoneally injected with 100 µL of PBS (placebo) or 100 µL of exponentially growing Phdp (1 × 10⁶ CFU/mL; infected). The blood, plasma, liver, and head kidney of six fish from each treatment were sampled immediately before infection and 3, 6, 9, 24 and 48 h after infection for the broad screening of fish immune and oxidative stress responses. Infected animals presented marked anaemia, neutrophilia and monocytosis, conditions that are correlated with an increased expression of genes related to inflammation and phagocytic activity. Similar studies with different fish species and bacteria can be useful for the definition of health biomarkers that might help fish farmers to prevent the occurrence of such diseases.     

3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by parenchymal scarring, leading progressively to alveolar architecture distortion, respiratory failure, and eventually death. Currently, there is no effective treatment for IPF. Previously, 3′5-dimaleamylbenzoic acid (3′5-DMBA), a maleimide, demonstrated pro-apoptotic, anti-inflammatory, and anti-cancer properties; however, its potential therapeutic effects on IPF have not been addressed. Bleomycin (BLM) 100 U/kg was administered to CD1 mice through an osmotic minipump. After fourteen days of BLM administration, 3′5-DMBA (6 mg/kg or 10 mg/kg) and its vehicle carboxymethylcellulose (CMC) were administered intragastrically every two days until day 26. On day 28, all mice were euthanized. The 3′5-DMBA effect was assessed by histological and immunohistochemical staining, as well as by RT-qPCR. The redox status on lung tissue was evaluated by determining the glutathione content and the GSH/GSSG ratio. 3′5-DMBA treatment re-established typical lung histological features and decreased the expression of BLM-induced fibrotic markers: collagen, α-SMA, and TGF-β1. Furthermore, 3′5-DMBA significantly reduced the expression of genes involved in fibrogenesis. In addition, it decreased reduced glutathione and increased oxidized glutathione content without promoting oxidative damage to lipids, as evidenced by the decrease in the lipid peroxidation marker 4-HNE. Therefore, 3′5-DMBA may be a promising candidate for IPF treatment.     

Pituitary Tumor-Transforming Gene 1/Delta like Non-Canonical Notch Ligand 1 Signaling in Chronic Liver Diseases

The management of chronic liver diseases (CLDs) remains a challenge, and identifying effective treatments is a major unmet medical need. In the current review we focus on the pituitary tumor transforming gene (PTTG1)/delta like non-canonical notch ligand 1 (DLK1) axis as a potential therapeutic target to attenuate the progression of these pathological conditions. PTTG1 is a proto-oncogene involved in proliferation and metabolism. PTTG1 expression has been related to inflammation, angiogenesis, and fibrogenesis in cancer and experimental fibrosis. On the other hand, DLK1 has been identified as one of the most abundantly expressed PTTG1 targets in adipose tissue and has shown to contribute to hepatic fibrosis by promoting the activation of hepatic stellate cells. Here, we extensively analyze the increasing amount of information pointing to the PTTG1/DLK1 signaling pathway as an important player in the regulation of these disturbances. These data prompted us to hypothesize that activation of the PTTG1/DLK1 axis is a key factor upregulating the tissue remodeling mechanisms characteristic of CLDs. Therefore, disruption of this signaling pathway could be useful in the therapeutic management of CLDs.     

Spanish Melon Landraces: Revealing Useful Diversity by Genomic,Morphological, and Metabolomic Analysis

Spain is a secondary centre of the diversification of the melon (Cucumis melo L.), with high diversity represented in highly appreciated landraces belonging to the Flexuosus and Ibericus groups. A collection of 47 accessions of Flexuosus, Chate, Piel de Sapo, Tendral, Amarillo, Blanco, and Rochet was analysed using a genotyping-by-sequencing (GBS) approach. A total of 66,971 quality SNPs were identified. Genetic analysis differentiated Ibericus accessions and exotic materials (Ameri, Momordica, Kachri, and Agrestis), while Flexuous accessions shared ancestry between them. Within the Ibericus group, no clear genomic distinction could be identified for the different landraces evaluated, with accessions of different landraces showing high genetic similarity. The morphological characterization confirmed that the external colour and fruit shape had been used as recognition patterns for Spanish melon landraces, but variability within a landrace exists. Differences were found in the sugars and acid and volatile profiles of the materials. Flexuosus and Chate melons at the immature commercial stage accumulated malic acid and low levels of hexoses, while Ibericus melons accumulated high contents of sucrose and citric acid. Specific trends could be identified in the Ibericus landraces. Tendral accumulated low levels of sugars and citric acid and high of malic acid, maintaining higher firmness, Rochet reached higher levels of sugars, and Amarillo tended to lower malic acid contents. Interestingly, high variability was found within landraces for the acidic profile, offering possibilities to alter taste tinges. The main volatile organic compounds (VOCs) in Flexuosus and Chate were aldehydes and alcohols, with clear differences between both groups. In the Ibericus landraces, general trends for VOC accumulation could be identified, but, again, a high level of variation exists. This situation highlights the necessity to develop depuration programs to promote on-farm in situ conservation and, at the same time, offers opportunities to establish new breeding program targets and to take advantage of these sources of variation.