Search Results (908)

The plant-specific TCP transcription factor family originated before the emergence of land plants. However, the timing of the appearance of their specific transcriptional repressor family, the TCP Interactor containing EAR motif protein (TIE), remains unknown. Here, through phylogenetic analyses, we traced the origin of the TIE family to the early evolution of the embryophyte, while an earlier diversification in algae cannot be ruled out. Strikingly, we found that the number of TIE members is highly constrained compared to the expansion of TCPs in angiosperms. We used co-expression data to identify potential TIE-TCP regulatory targets across Arabidopsis thaliana and rice. Notably, the expression pattern between these species is remarkably similar. TCP Class I and Class II genes formed two distinct clusters, and TIE genes cluster within the TCP Class I group. This study provides a comprehensive evolutionary analysis of the TIE family, shedding light on its conserved role in the regulation of gene transcription in flowering plant development. Full article

Cadmium (Cd) pollution poses a serious threat to freshwater ecosystems. The freshwater mussel Anodonta woodiana is increasingly used as a bioindicator for monitoring Cd pollution in aquatic environments. However, the primary routes of Cd accumulation in A. woodiana remain unclear, and the molecular regulatory mechanisms underlying Cd accumulation are poorly understood. To address these gaps, this study employed a novel stable isotope dual-tracer technique to trace Cd from water (waterborne ¹¹²Cd) and the green alga Chlorella vulgaris (dietary ¹¹³Cd) during the simultaneous exposure experiment. Comparative transcriptomic analysis was then conducted to characterize molecular responses in A. woodiana following Cd exposure. The results showed that although newly accumulated ¹¹²Cd and ¹¹³Cd increased with exposure concentration and duration, the relative importance of ¹¹²Cd (91.6 ± 2.8%) was significantly higher than that of ¹¹³Cd (8.4 ± 2.8%) (p < 0.05). Cd exposure induced differentially expressed genes primarily enriched in the metabolic processes, cellular processes, and/or the ubiquitin-mediated proteolysis pathway. Within the ubiquitin-mediated proteolysis pathway, TRIP12 (E3 ubiquitin-protein ligase TRIP12) and Cul5 (cullin-5) were significantly upregulated. The findings will provide critical insights for interpreting Cd biomonitoring data in freshwater environments using mussels as bioindicators. Full article

The c-ErbB receptor family is a fundamental cell signaling system that regulates cell proliferation, motility, apoptosis, differentiation, and other key cellular functions. Overexpressed and mutated in some tumors, c-ErbB receptors play a pivotal role in their progression but are also present in many non-malignant cells, including those that are promising from the point of view of regenerative medicine, such as mesenchymal stromal cells (MSCs). The role of c-ErbB receptors in these cells is not clearly understood, and the data on their expression are sporadic. Therefore, the systemic characterization of c-ErbB receptor family expression in MSCs from a wide range of tissues is of high priority. Here, using RT-qPCR and Western blotting analysis, we evaluated the c-ErbB receptors expression pattern at the mRNA and protein levels in human MSCs isolated from six different tissues. We found that MSCs possess considerable EGFR and HER2 mRNA levels comparable to those in some malignant cells while showing trace HER3 and HER4 expression. However, EGFR but not HER2 was detected in MSCs at the protein level. We also show that the absence of HER2 protein is not associated with its rapid lysosomal degradation. We conclude that c-ErbB signaling in human MSCs is exclusively mediated by EGFR. Full article

The common octopus (Octopus vulgaris) supports one of the most valuable small-scale fisheries in Portugal, particularly in the Algarve region, with substantial socioeconomic implications. This species holds significant potential for human consumption due to its low lipid content, favorable fatty acid profile, high-quality protein, and essential microelements. This study aimed to provide a comprehensive characterization of octopus specimens landed in two key Algarve fishing areas—Barlavento/Windward (Alvor Harbour) and Sotavento/Leeward (Fuzeta Harbour). We assessed their nutritional value, focusing on protein quality, lipid indexes, trace minerals, and essential vitamins, as well as overall safety and quality. All regulated contaminants and additional potential risks were also evaluated, yielding fully satisfactory safety results. The research was conducted within the framework of the European Sea2See project, which aims to enhance consumer trust and acceptance of sustainably harvested or farmed seafood in Europe. Our findings demonstrate that Algarve octopus is a nutritionally rich seafood product, promoting cardiovascular health and general well-being. Full article

Prenatal and postnatal skeletal muscle development in ruminants is coordinated by interactions between genetic, nutritional, epigenetic, and endocrine factors. This review focuses on the influence of maternal nutrition during gestation on fetal myogenesis, satellite cell dynamics, and myogenic regulatory factors expression, including MYF5, MYOD1, and MYOG. Studies in sheep and cattle indicate that nutrient restriction or overnutrition alters muscle fiber number, the cross-sectional area, and the transcriptional regulation of myogenic genes in offspring. Postnatally, muscle hypertrophy is primarily mediated by satellite cells, which are activated via PAX7, MYOD, and MYF5, and regulated through mechanisms such as CARM1-induced chromatin remodeling and miR-31-mediated mRNA expression. Hormonal signaling via the GH–IGF1 axis and thyroid hormones further modulate satellite cell proliferation and protein accretion. Genetic variants, such as myostatin mutations in Texel sheep and Belgian Blue cattle, enhance muscle mass but may compromise reproductive efficiency. Nutritional interventions, including the plane of nutrition, supplementation strategies, and environmental stressors such as heat and stocking density, significantly influence muscle fiber composition and carcass traits. This review provides a comprehensive overview of skeletal muscle programming in ruminants, tracing the developmental trajectory from progenitor cell differentiation to postnatal growth and maturation. These insights underscore the need for integrated approaches combining maternal diet optimization, molecular breeding, and precision livestock management to enhance muscle growth, meat quality, and production sustainability in ruminant systems. Full article

Tailoring culture media and supplementation strategies to the specific requirements of a target product is essential for enhancing microbial production efficiency. This work addresses an unexplored aspect of K. phaffii cultivation: optimizing culture media for metabolite production from xylose, diverging from the conventional focus on recombinant protein expression and the use of glycerol or methanol as primary substrates. Ethylene glycol biosynthesis in an engineered K. phaffii strain was improved by evaluating media and nutrient supplementation. Among the seven evaluated formulations, FM22 and d’Anjou were the most effective, with inositol and thiamine dichloride playing key roles in enhancing production. Salt concentrations in both media were optimized using Central Composite Design (CCD), reducing complexity while increasing yields. Ethylene glycol production increased by 54% in FM22 and 21% in d’Anjou, accompanied by a threefold and 26% reduction in the total salt content, respectively. The vitamin solution was streamlined from seven to two components, each at half the standard concentration. Trace element solutions were reduced to 25% of the original volume without compromising productivity. These findings underscore the dual benefit of culture medium optimization: improved ethylene glycol yields and simplified formulations, establishing a foundation for the development of more efficient and cost-effective bioprocesses using K. phaffii. Full article

This study explores the effects of selenium-enriched yeast supplementation on growth-related and immune-related gene expression in C. gigas, aiming to support feed optimization in oyster aquaculture. Selenium, an essential trace element, is vital for growth, immune function, and metabolism in animals. Selenium-enriched yeast, an organic form, offers superior bioavailability, enabling efficient absorption and utilization. C. gigas, a commercially significant marine shellfish, is rich in protein and nutrients, but the effects of selenium on mollusks remain insufficiently explored. In this study, oysters were divided into three groups: a control group without selenium (THNP), a 2 ppm selenium group (THMP), and a 4 ppm selenium group (THHP). Transcriptome sequencing yielded 388,679,026 clean reads. GO and KEGG enrichment analyses identified key metabolic signaling pathways, and a PPI analysis was performed on the translation products of DEGs involved in the KEGG pathways. qRT-PCR validated the expression of principal DEGs. The combined results of enrichment and PPI analyses highlighted pathways such as glutathione metabolism and collagen signaling. Additionally, three hub genes—FASN, HRAS, and ABCG5—were identified as central to the selenium response. These findings enhance the understanding of selenium’s molecular impact on oysters and support its application in aquaculture. Full article

Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein. The soluble form of PD-L1 (sPD-L1) and PD-L1 derived from small extracellular vesicles (sEVPD-L1) are promising cancer biomarkers. While sEVPD-L1 in particular may contribute to immune evasion and is associated with a poor prognosis, it exists only in trace amounts, making it difficult to detect using conventional enzyme-linked immunosorbent assay (ELISA) methods. Therefore, we developed an ultrasensitive detection method, TN-cyclon™. The TN-cyclon™ method combines sandwich ELISA with enzyme cycling amplification. We applied TN-cyclon™ to measure recombinant PD-L1 protein and sEVPD-L1 in serum samples from cancer patients and healthy donors. Recombinant PD-L1 protein was measured with an ultrasensitive detection limit of 0.172 pg/mL. In clinical specimens, sEVPD-L1 levels were significantly higher in lung cancer patients than in healthy donors, whereas sPD-L1 levels measured with a conventional ELISA did not differ significantly between groups. Our results demonstrated that the TN-cyclon™ method exhibits a 20-fold increase in sensitivity compared to a conventional ELISA. Although this is a pilot study, our new assay enables the detection of very low concentrations of sEVPD-L1 in serum that can be used to evaluate the predictive and prognostic performance of sEVPD-L1 in lung cancer patients in future studies. Full article

Structural analysis of motoneuron somas and their associated proteins via immunohistochemistry (IHC) remains tedious and subjective, requiring costly software or adapted 2D manual methods that lack reproducibility and analytical rigor. Yet, neurodegenerative disease and aging research demands precise structural comparisons to elucidate mechanisms driving neuronal degeneration. To address this need, we developed a novel algorithm that automates repetitive and subjective IHC analysis tasks, enabling thorough, objective, blinded, order-agnostic, and reproducible 3D batch analysis. With no manual tracing, the algorithm produces 3D Cartesian reconstructions of motoneuron somas from 60× IHC images of mouse lumbar spinal tissue. From these reconstructions, it measures 3D soma volume and efficiently quantitates net somatic protein expression and macro-cluster size. In this validation study, we applied the algorithm to assess soma size and C-bouton expression in various healthy control mice, comparing its measurements against manual measurements and across multiple algorithm users to confirm its accuracy and reproducibility. This novel, customizable tool enables efficient and high-fidelity 3D motoneuron analysis, replacing tedious, qualitative, cell-by-cell manual tuning with automatic threshold adaptation and quantified batch settings. For the first time, we attain reproducible results with quantifiable accuracy, exhaustive sampling, and a high degree of objectivity. Full article

Calcium plays a major role in all cellular functions, and its regulation is important in all aspects of human health. This key role calcium plays in cell function can be traced to its unique molecular coordination geometry, which is often overlooked in understanding calcium function. In this review, we integrate calcium’s ability to form various complexes with proteins and small molecules with its role as a key signaling atom. We argue that calcium’s ability to vary its coordination structures, compared to magnesium’s rigid geometry, explains its importance in biological functions. By examining calcium-mediated proteins, such as those containing EF-hand domains and those that assemble and stabilize the extracellular matrix in tissue organization, we demonstrate how calcium’s varied geometric coordination serves as both a signaling molecule and a regulator of physiological homeostasis. Full article

This study investigates the nutritional and chemical profile of cricket (Acheta domesticus) flour, evaluating its potential as a sustainable and highly nutritious food source. Cricket flour, with a protein content of approximately 60%, offers a significantly higher nutritional value compared to many traditional food sources. It is particularly rich in essential amino acids, making it a valuable and sustainable protein alternative. Additionally, the flour is rich in minerals such as potassium, calcium, magnesium, copper, and zinc. The administration of 100 g of cricket flour would exceed the recommended daily intake for adults for most nutrients, making its incorporation into more traditional foods such as bread and pasta at low percentages feasible, easily compensating for any imbalances and increasing their nutritional values. We found that an addition of a mere 10% of cricket flour to produce an experimental pasta fulfilled half of the recommended daily intake values for protein, lipids, and minerals. Chemical analyses of the pure cricket flour revealed only trace amounts of polycyclic aromatic hydrocarbons (PAHs) and linear alkanes, with concentrations well below safety thresholds established for other food categories, indicating that cricket flour is safe for human consumption. The study’s findings confirm that cricket flour is a promising sustainable protein source, and its integration into classic foods could safely contribute to alleviating iron and copper deficiencies as well as malnutrition. Full article

Microglia-mediated neuroinflammation is a key driver of Alzheimer’s disease (AD). In AD, microglia are activated and trigger an increased secretion of pro-inflammatory factors. Rhein, an anthraquinone compound extracted from rhubarb, has been shown to reduce the secretion of pro-inflammatory cytokines including TNF-α and IL-1β in activated microglia. However, the mechanism of rhein on microglia-mediated neuroinflammation and neuronal damage in AD remains unclear. In this study, we found that rhein improved behavioral abnormalities in AD rats and reduced the levels of inflammatory factors such as IL-1β, iNOS, and NO in the brain of AD rats. In the LPS-induced microglial model, rhein significantly reduced the levels of inflammatory factors to improve neuroinflammation. Untargeted metabolomics showed that the reprogramming of glutamine metabolism occurred in M1 microglia. Targeted metabolomics and ¹³C, ¹⁵N isotope tracing experiments demonstrated that rhein regulated the metabolite levels in the glutamine–aspartate–arginine metabolic pathway. Meanwhile, the upregulated expression of proteins such as GLS1 and GOT1 within this pathway was reversed by rhein. Furthermore, we found that the glutamine–aspartate–arginine metabolic pathway regulates the production of nitric oxide (NO, a neuroinflammatory mediator). Rhein alleviates neuronal damage by inhibiting the glutamine–aspartate–arginine–NO metabolic pathway. In conclusion, our study shows that rhein may inhibits NO production by regulating the glutamine–aspartate–arginine metabolic pathway in activated microglia, thereby inhibiting the neuroinflammation and neuronal damage in AD. Full article

Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of the virus continue to pose substantial challenges. Methods: In this review paper, we aim to provide a comprehensive review of previous vaccine candidates and the progress made in HIV vaccine clinical trials, spanning from the late 1990s to 2025. PubMed and ClinicalTrials.gov were searched for English-language Phase 1–3 HIV vaccine trials published from 1990 to March 2025. After de-duplication, titles/abstracts and then full texts were screened; trial phase, regimen, immunogenicity, efficacy, and correlates were extracted into a structured spreadsheet. Owing to platform heterogeneity, findings were synthesized narratively and arranged chronologically to trace the evolution of vaccine strategies. Results: Early vaccine trials demonstrated that a protein subunit vaccine failed to protect against infection, revealing the complexity of HIV evasion strategies and shifting the focus to a comprehensive immune response, including both antibody and T-cell responses. Trials evaluating the role of viral vectors in generating cell-mediated immunity were also insufficient, and suggested that targeting T cell response alone was not enough. In 2009, the RV144 trial made a breakthrough by showing partial protection against HIV infection and providing the first indication of efficacy. This partial success influenced subsequent trials, prompting researchers to further explore the complex immune response required for protection and consider combinations of vaccine technologies to achieve robust, long-lasting immunity. Conclusion: Despite setbacks, decades of rigorous efforts have provided significant contributions to HIV vaccine discovery and development, offering hope for preventing and protecting against HIV infection. The field remains active by continuing to advance our understanding of the virus, refining vaccine strategies, and employing novel technologies. Full article

Pollen, the male gametophyte of flowering plants, is collected by honeybees as a primary source of protein and converted into bee pollen through the enzymatic activity of digestive secretions. The nutrients in bee pollen are available in amounts well beyond those of proteins, comprising macronutrients such as carbohydrates, lipids and dietary fiber, as well as micronutrients such as minerals, vitamins, organic acids, and phenolic compounds. This study aimed to determine the macro and trace mineral content of bee pollen from different botanical and geographical origins, and to assess their bioaccessibility through simulated in vitro digestion, their dietary contribution, and potential health risks. Seven bee pollen samples were investigated, three with a monofloral origin of above 80%, from Nigella spp., Helianthus annuus and Castanea sativa, and four with a multifloral origin. Mineral composition revealed potassium as the most abundant element, while iron, manganese, and copper were found at trace levels. Castanea sativa pollen had the highest overall mineral content, whereas Nigella spp. showed the lowest values for calcium, magnesium, and copper. The bioaccessibility of bee pollen was highest during the gastric phase for most minerals except copper, where most of the samples peaked in the intestinal phase. Overall, mineral bioaccessibility after simulated digestion followed the order K > Mg > Cu > Ca > Mn > Fe > Zn. While for manganese, the consumption of bee pollen showed the highest contribution to recommended dietary intake (16% for women and 12% for men), calcium had the lowest, with less than 1% of the RDA at a consumption level of 40 g/day. Health risk assessment confirmed that consuming 40 g/day of bee pollen poses no risk because the target hazard quotient and hazard index are below the risk threshold of 1.0. Full article

Zn is a trace element necessary for the functioning of about 300 enzymes. It plays a biochemical, structural, and regulatory role. It participates in the immune response, proper functioning of the endocrine system, and regulation of gene expression. Its deficiencies are most often caused by the mismatch between dietary intake and the body’s needs. Bioavailability of zinc depends on interactions with other food components. Phytates negatively affect this element’s absorption, whereas proteins, peptides, and amino acids increase its bioavailability. It has been proven that organic forms of zinc are better absorbed than inorganic compounds, like zinc oxide and sulfate. Amino acid combinations with zinc can use amino acid transporters in the absorption process. Estimation of Zn bioavailability and bioaccessibility are based on in vivo and in vitro studies, each having their advantages and disadvantages. The current review aims to gather and summarize recent research on the dietary role of Zn, especially data on bioavailability from food substances promoting/inhibiting absorption, and the latest methods for determining the level of bioavailability of this nutrient. Full article