Search Results (4,534)

Sprouty-related proteins with enabled/vasodilator-stimulated phosphoprotein homology 1 (EVH1) domain (SPREDs) are negative regulators of the Ras/MAPK signaling pathway and are known to modulate developmental and endocrine processes. While the roles of SPRED1 and SPRED2 are increasingly understood, the physiological relevance of SPRED3 remains elusive. To elucidate its function, we generated SPRED3 knockout (KO) mice and performed phenotypic, molecular, and hormonal analyses. SPRED3-deficient mice exhibited growth retardation and a non-Mendelian genotype distribution. X-Gal staining revealed Spred3 promoter activity in the thyroid, adrenal gland, pituitary, cerebral cortex, and kidney. Hormonal profiling identified elevated thyroid-stimulating hormone (TSH) and reduced thyroxine (T₄) levels, indicating primary hypothyroidism. Thyroidal extracellular signal-regulated kinase (ERK) signaling was mildly reduced in SPRED3 KO mice, and immunoblotting revealed altered expression of autophagy regulators, including reduced sequestosome 1 (p62), increased autophagy-related gene 5 (ATG5), as well as an elevated microtubule-associated protein 1 light chain 3 (LC3) II/I ratio and a decreased pBeclin/Beclin ratio in SPRED3 KO mice. Our findings indicate that SPRED3 is involved in thyroidal homeostasis and plays a regulatory role in autophagy processes within the thyroid gland. Full article

This study introduces xylitol, a natural compound, as a multifunctional additive to enhance the performance of alkali-activated slag/fly ash materials (AASFMs). A systematic investigation was conducted to elucidate xylitol’s mechanism in modifying AASFM properties, including fresh behavior, hydration kinetics, compressive strength, and autogenous shrinkage. The experimental findings demonstrated that xylitol significantly delayed early-age hydration while promoting more extensive hydration at later stages. Specifically, the initial and final setting times of AASFM pastes were extended by 640% and 370%, respectively, and paste flowability increased by 30%. At a 0.2% dosage, xylitol markedly reduced porosity and refined the microstructure of AASFMs, leading to improved mechanical properties. The 3-day and 28-day compressive strengths were enhanced by 39.8% and 39.7%, respectively, while autogenous shrinkage was suppressed by 61.4%. These results demonstrate the multifunctional potential of xylitol in AASFMs, serving as an effective retarder, plasticizer, strength enhancer, and shrinkage reducer. Notably, the refined pore structure induced by xylitol may also mitigate the risks of the alkali–silica reaction, though further durability validation is warranted. Full article

The large yellow croaker (Larimichthys crocea) is susceptible to microbial contamination during storage due to its high protein and moisture contents. This study was designed to find a new way to reduce bacteria in large yellow croakers by combining slightly acidic electrolyzed water (SAEW) with nano-bubble (NB) technology. Exploring the effects of available chlorine concentration (ACC), processing time, and water temperature on the bacteria reduction effect of the SAEW-NB treatment for large yellow croakers. Also, the effects of the SAEW-NB combined treatment on sensory evaluation, total viable counts (TVCs), total volatile basic nitrogen (TVB-N), texture, taste profile, and volatile flavor compounds of large yellow croakers were analyzed during the storage period at 4 °C. The results show that the SAEW-NB treatment achieved significantly enhanced microbial reduction compared to individual treatments. Under the conditions of a 4 °C water temperature, 40 mg/L ACC, and 15 min treatment, the SAEW-NB treatment inhibited the increases in physical and chemical indexes such as TVC and TVB-N, maintained the fish texture, and delayed the production of off-flavor volatiles such as aldehydes, alcohols, esters, and ketones, compared with the control group (CG) during storage at 4 °C. In conclusion, the SAEW-NB treatment could better retard fish spoilage, extending the shelf life by approximately 2 days. It might be a promising new industrial approach for large yellow croakers’ storage. Full article

Tetrabromobisphenol A (TBBPA), a widely utilised brominated flame retardant, demonstrates toxicological effects in aquatic organisms. Tea polyphenols (TPs), natural compounds found in tea leaves, exhibit both antioxidant and anti-inflammatory activities. The kidney is one of the major metabolic organs in common carp and serves as a target organ for toxic substances. This study evaluated the therapeutic potential of TPs in mitigating TBBPA-induced nephrotoxicity in common carp. Common carp were exposed to 0.5 mg/L TBBPA in water and/or fed a diet supplemented with 1 g/kg TPs for 14 days. In vitro, primary renal cells were treated with 60 μM TBBPA and/or 2.5 μg/L TPs for 24 h. Methods included histopathology, TUNEL assay for apoptosis, ROS detection, and molecular analyses. Antioxidant enzymes (SOD, CAT) and inflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified using ELISA kits. Results showed that TBBPA induced oxidative stress, and activated the ROS-PI3K/AKT-NF-κB pathway, thereby resulting in inflammatory responses. TBBPA upregulated apoptosis-related genes (Caspase-3, Bax, and Bcl-2) and induced apoptosis. TBBPA upregulated the expression of RIPK3/MLKL, thereby exacerbating necroptosis. TPs intervention significantly mitigated these effects by reducing ROS, suppressing NF-κB activation, and restoring antioxidant enzyme activities (SOD, CAT). Moreover, TPs attenuated apoptosis and necrosis in the carp kidney, thereby enhancing the survival ability and immunity of common carp. Full article

Wheat (Triticum aestivum L.) is a crucial global food crop. The intensive crop farming, monoculture cultivation, and impact of climate change affect the susceptibility of wheat cultivars to biotic stresses, mainly caused by soil fungal pathogens, especially those belonging to the genus Fusarium. This situation threatens yield and grain quality through root and crown rot. While conventional chemical fungicides face resistance issues and environmental concerns, biological alternatives like seed priming with natural metabolites are gaining attention. Polyamines, including putrescine, spermidine, and spermine, are attractive priming agents influencing plant development and abiotic stress responses. Spermine in particular shows potential for in vitro antifungal activity against Fusarium. Optimising spermine concentration for seed priming is crucial to maximising protection against Fusarium infection while ensuring robust plant growth. In this research, we explored the potential of the polyamine spermine as a seed treatment to enhance wheat resilience, aiming to identify a sustainable alternative to synthetic fungicides. Our findings revealed that a six-hour seed soak in spermine solutions ranging from 0.5 to 5 mM did not delay germination or seedling growth. In fact, the 5 mM concentration significantly stimulated root weight and length. In complementary in vitro assays, we evaluated the antifungal activity of spermine (0.5–5 mM) against three Fusarium species. The results demonstrated complete inhibition of Fusarium culmorum growth at 5 mM spermine. A less significant effect on Fusarium graminearum and little to no impact on Fusarium oxysporum were found. The performed analysis revealed that the spermine had a fungistatic effect against the pathogen, retarding the mycelium growth of F. culmorum inoculated on the seed surface. A pot experiment with Bulgarian soft wheat cv. Sadovo-1 was carried out to estimate the effect of seed priming with spermine against infection with isolates of pathogenic fungus F. culmorum on plant growth and disease severity. Our results demonstrated that spermine resulted in a reduced distribution of F. culmorum and improved plant performance, as evidenced by the higher fresh weight and height of plants pre-treated with spermine. This research describes the efficacy of spermine seed priming as a novel strategy for managing Fusarium root and crown rot in wheat. Full article

Sewage sludge (SS) is commonly applied as a soil amendment. This practice has raised concern about the dissemination of emerging pollutants (EPs). EPs include compounds such as flame retardants, plasticizers, pharmaceuticals, and personal care products, among others, which may pose risks to human health and ecosystems. The complexity of the SS matrix, combined to the absence of an international legislation framework, makes it necessary to evaluate the techniques available for detecting these contaminants. Detection is typically performed using sensitive analytical techniques; however, the extraction strategy selected remains a crucial step. This review aims to compile different methodologies for the determination of EPs in SS, focusing on extraction strategies reported between 2010 and 2025. Ultrasound-assisted extraction (UAE), pressurized liquid extraction (PLE), and microwave-assisted extraction (MAE) are the most widely used strategies for EPs. UAE is considered the most preferable option, as it enables the extraction of a wide range of compounds without the need for expensive equipment. Among novel techniques, the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method is especially promising, as it is applicable to multiple target compounds. This review provides up-to-date information that can support the development of routine and standardized methodologies for the characterization of EPs in SS. Full article

Lipid nanoparticle (LNP)-based delivery systems are promising tools for advancing RNA-based therapies. However, there are underlying challenges for the oral delivery of LNPs. In this study, we optimized an LNP formulation, which we encapsulated in a pH-sensitive Eudragit^® S 100 (Eu) coating. LNPs were prepared using the DLin-MC3-DMA ionizable lipid, cholesterol, DMG-PEG, and DSPC at a molar ratio of 50:38.5:10:1.5. LNPs were coated with 1% Eu solution via nanoprecipitation using 0.25% acetic acid to get Eu-coated LNPs (Eu-LNPs). Particle characteristics of LNPs were determined by using dynamic light scattering (DLS). Ribogreen and agarose gel retardation assays were used to evaluate nucleic acid entrapment and stability. LNPs and Eu-LNPs were ~120 nm and 4.5 μm in size, respectively. Eu-LNPs decrease to an average size of ~191 ± 22.9 nm at a pH of 8. Phosphate buffer (PB)-treated and untreated Eu-LNPs and uncoated LNPs were transfected in HEK-293 cells. PB-treated Eu-LNPs showed significant transfection capability compared to their non-PB-treated counterparts. Eu-LNPs protected their nucleic acid payloads in the presence of a simulated gastric fluid (SGF) with pepsin and maintained transfection capacity following SGF or simulated intestinal fluid. Hence, Eu coating is a potentially promising approach for the oral administration of LNPs. Full article

This study aimed to investigate the efficacy of a composite coating composed of 150 mg/L ε-Poly-L-lysine (ε-PL) and 5 g/L chitosan (CTS) in extending the shelf life and maintaining the postharvest quality of fresh Tremella fuciformis. Freshly harvested T. fuciformis were treated by surface spraying, with distilled water serving as the control. The effects of the coating on storage quality, physicochemical properties, reactive oxygen species (ROS) metabolism, and membrane lipid metabolism were evaluated during storage at (25 ± 1) °C. The results showed that the ε-PL/CTS composite coating significantly retarded quality deterioration, as evidenced by reduced weight loss, maintained whiteness and color, and higher retention of soluble sugars, soluble solids, and soluble proteins. The coating also effectively limited water migration and loss. Mechanistically, the coated T. fuciformis exhibited enhanced antioxidant capacity, characterized by increased superoxide anion (O₂⁻) resistance capacity, higher activities of antioxidant enzymes (SOD, CAT, APX), and elevated levels of non-enzymatic antioxidants (AsA, GSH). This led to a significant reduction in malondialdehyde (MDA) accumulation, alongside improved DPPH radical scavenging activity and reducing power. Furthermore, the ε-PL/CTS coating preserved cell membrane integrity by inhibiting the activities of lipid-degrading enzymes (lipase, LOX, PLD), maintaining higher levels of key phospholipids (phosphatidylinositol and phosphatidylcholine), delaying phosphatidic acid accumulation, and consequently reducing cell membrane permeability. In conclusion, the ε-PL/CTS composite coating effectively extends the shelf life and maintains the quality of postharvest T. fuciformis by modulating ROS metabolism and preserving membrane lipid homeostasis. This study provides a theoretical basis and a practical approach for the quality control of fresh T. fuciformis. Full article

Triphenyl phosphate (TPhP) is a widely used organophosphate flame retardant and plasticizer, raising concerns over its health impacts. This study examined the effects of embryonic TPhP exposure on axial skeletal development and metabolism in medaka (Oryzias latipes), a vertebrate fish model relevant to human bone biology. Medaka embryos were exposed to 1 µM TPhP and assessed through early larval stages. TPhP impaired vertebral ossification, causing shortened centra and reduced cartilage in the caudal complex, alongside disrupted distribution of osteoblast-lineage cells. Key osteogenic genes were significantly downregulated at 14 days post fertilization, and transcriptomic analysis revealed altered mitochondrial pathways linked to skeletal disorders. Functionally, TPhP-exposed larvae showed reduced caudal fin regeneration and decreased metabolic rate and oxygen consumption, consistent with mitochondrial dysfunction. These findings indicate that TPhP disrupts bone development and metabolism by affecting osteoblast differentiation and mitochondrial regulation, highlighting the value of small fish models for studying environmental toxicants and bone metabolic disease risk. Full article

Maritime corrosion is a global problem often retarded through protective coatings containing corrosion inhibitors (CIs). ZnAl layered double hydroxides (LDH) have been used to immobilize CIs, which can reduce their early leaching and, thus, foster long-term corrosion protection. However, the environmental behavior of these nanomaterials remains largely unknown, particularly in the context of global changes. The present study aims to assess the environmental behavior of four anti-corrosion nanomaterials in an ocean acidification scenario (IPCC SSP3-7.0). Three different concentrations of the nanostructured CIs (1.23, 11.11, and 100 mg L⁻¹) were prepared and maintained at 20 °C and 30 °C in artificial salt water (ASW) at two pH values, with and without the presence of organic matter. The nanomaterials’ particle size and the release profiles of Al³⁺, Zn²⁺, and anions were monitored over time. In all conditions, the hydrodynamic size of the dispersed nanomaterials confirmed that the high ionic strength favors their aggregation/agglomeration. In the presence of organic matter, dissolved Al³⁺ increased, while Zn²⁺ decreased, and increased in the ocean acidification scenario at both temperatures. CIs were more released in the presence of humic acid. These findings demonstrate the influence of the tested parameters in the nanomaterials’ environmental behavior, leading to the release of metals and CIs. Full article

Miller–Dieker Syndrome (MDS) is a rare neurodevelopmental disorder caused by a heterozygous deletion of approximately 26 genes within the MDS locus of human chromosome 17. MDS, which affects 1 in 100,000 babies, can lead to a range of phenotypes, including lissencephaly, severe neurological defects, distinctive facial abnormalities, cognitive impairments, seizures, growth retardation, and congenital heart and liver abnormalities. One hallmark feature of MDS is an unusually smooth brain surface due to abnormal neuronal migration during early brain development. Several genes located within the MDS locus have been implicated in the pathogenesis of MDS, including PAFAH1B1, YWHAE, CRK, and METTL16. These genes play a role in the molecular and cellular pathways that are vital for neuronal migration, the proper development of the cerebral cortex, and protein translation in MDS. Improved model systems, such as MDS patient-derived organoids and multi-omics analyses indicate that WNT/β-catenin signaling, calcium signaling, S-adenosyl methionine (SAM) homeostasis, mammalian target of rapamycin (mTOR) signaling, Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and others are dysfunctional in MDS. This review of MDS integrates details at the clinical level alongside newly emerging details at the molecular and cellular levels, which may inform the development of novel therapeutic strategies for MDS. Full article

Halogenated flame retardants have been amongst the most widely used and effective solutions for enhancing fire resistance. However, their use is currently strictly regulated due to serious health and environmental concerns. In this context, phosphorus-based and mineral flame retardants have emerged as promising alternatives. Despite this, their combined use is neither straightforward nor guaranteed to be effective. This study scrutinizes the interactions between these two classes of flame retardants (FR) through a systematic analysis aimed at elucidating the antagonistic pathways that arise from their coexistence. Specifically, this study focuses on two inorganic fillers, mineral huntite and chemically precipitated magnesium hydroxide, both of which produce basic oxides upon thermal decomposition. These fillers were incorporated into a poly(butylene terephthalate) (PBT) matrix to be utilized as advanced-mattress FR coating fabric and were subjected to a series of flammability tests. The pyrolysis products of the prepared polymeric composite compounds were isolated and thoroughly characterized using a combination of analytical techniques. Thermogravimetric analysis (TGA) and differential thermogravimetric analysis (dTGA) were employed to monitor decomposition behavior, while the char residues collected at different pyrolysis stages were examined spectroscopically, using FTIR-ATR and Raman spectroscopy, to identify their structure and the chemical reactions that led to their formation. X-ray diffraction (XRD) experiments were also conducted to complement the spectroscopic findings in the chemical composition of the resulting char residues and to pinpoint the different species that constitute them. The morphological changes of the char’s structure were monitored by scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS). Finally, the Limited Oxygen Index (LOI) and UL94 (vertical sample mode) methods were used to assess the relative flammability of the samples, revealing a significant drop in flame retardancy when both types of flame retardants are present. This reduction is attributed to the neutralization of acidic phosphorus species by the basic oxides generated during the decomposition of the basic inorganic fillers, as confirmed by the characterization techniques employed. These findings underscore the challenge of combining organophosphorus with popular flame-retardant classes such as mineral or basic metal flame retardants, offering insight into a key difficulty in formulating next-generation halogen-free flame-retardant composite coatings. Full article

Intrauterine growth retardation (IUGR) is highly prevalent in modern swine production, and many affected piglets survive past weaning and are raised for commercial pork production. This review summarizes the current understanding of the physiological challenges of IUGR piglets from a molecular perspective and evaluates recent advances in nutritional strategies aimed at mitigating their negative outcomes. Molecular approaches, including omics technologies and targeted analyses, have been employed to investigate the physiological characteristics of IUGR piglets. These approaches consistently show that IUGR piglets exhibit systemic dysfunction, including compromised gut health, increased inflammation and oxidative stress, and impaired function of multiple organs such as the intestine, liver, kidney, and immune-related tissues. Moreover, IUGR piglets often display poor muscle development and meat quality. The multifactorial nature of these issues suggests that targeting a single physiological parameter may be insufficient, and comprehensive interventions are needed to address the widespread effects of IUGR. Promising nutritional strategies such as supplementation with polyphenol-rich plant extracts, amino acids, and probiotics have demonstrated potential in improving gut integrity, beneficially modulating microbiota, and enhancing the overall health and performance of IUGR piglets. By supporting the systemic recovery of IUGR piglets, nutritional interventions could improve overall productivity in swine production systems. Full article

The maternal–fetal environment is influenced by multiple factors, including nutrition and environmental contaminants, which can impact long-term development. Perinatal exposure to organophosphate flame retardants (OPFRs) disrupts energy homeostasis and causes maladaptive behaviors in mice. Maternal obesity affects development by impairing blood–brain barrier (BBB) formation, influencing brain regions involved in energy regulation and behavior. This study examined the combined effects of maternal obesity and perinatal OPFR treatment on offspring development. Female mice were fed either a low-fat (LFD) or a high-fat diet (HFD) for 8 weeks, mated, and treated with either sesame oil or an OPFR mixture (tris(1,3-dichloro-2-propyl)phosphate, tricresyl phosphate, and triphenyl phosphate, 1 mg/kg each) from gestational day 7 to postnatal day 14. Results showed that both maternal diet and OPFR treatment disrupted blood–brain barrier integrity, energy balance, and reproductive gene expression in the hypothalamus of neonates. The expression of hepatic genes related to lipid and xenobiotic metabolism was also altered. In adulthood, LFD OPFR-treated female offspring exhibited increased avoidance behavior, while HFD OPFR-treated females demonstrated memory impairments. Metabolic assessments revealed decreased energy expenditure and nighttime activity in LFD OPFR-treated females. These findings suggest that maternal diet and OPFR treatment alter hypothalamic and liver gene expression in neonates, potentially leading to long-term metabolic and behavioral changes. Full article

Tetrabromobisphenol A (TBBPA) is a brominated flame retardant widely used in consumer products. TBBPA is often detected in soil, water, organisms, and even in human blood and breast milk. Hence, it is accessible to developing fetuses and nursing offspring after maternal exposure. The reported evidence for the endocrine disruption of TBBPA in the brain has raised concerns regarding its effects on neurodevelopmental and behavioral functions. This study investigated the effects of TBBPA exposure on neurodevelopment. A cell-based developmental neurotoxicity assay was performed to determine whether TBBPA is a developmental neurotoxicant. The assay revealed TBBPA to be a developmental neurotoxicant. C57BL/6N maternal mice were administered TBBPA at 0, 0.24, and 2.4 mg/kg during pregnancy and lactation, and their offspring underwent behavioral testing. The behavioral experiments revealed sex-specific effects. In females, only a deterioration of the motor ability was observed. In contrast, deteriorations in motor function, memory, and social interaction were noted in males. Furthermore, we validated changes in the expression of genes associated with behavioral abnormalities, confirming that perinatal exposure to TBBPA, at the administered doses, can affect neurodevelopment and behavior in offspring. These findings highlight the need for more in-depth and multifaceted research on the toxicity of TBBPA. Full article