Search Results (6,505)

Salmonella enterica serovar Typhimurium (ST) is an intracellular pathogen that survives within macrophages and disseminates to systemic organs, thereby evading host immune defenses. Previous studies have shown that the probiotic yeast Saccharomyces boulardii CNCM I-745 improves survival in ST-infected mice, reduces bacterial translocation, and modulates cytokine expression, including the upregulation of interferon-γ and the downregulation of interleukin-10, both of which are involved in the regulation of inducible nitric oxide synthase (iNOS), a key mediator of macrophage antimicrobial activity. The present study was designed to investigate the transcriptional regulation of iNOS and associated antimicrobial responses in ST-infected RAW264.7 murine macrophages pretreated or cotreated with S. boulardii. Gene expression levels of iNOS and selected cytokines were analyzed in RT-qPCR assays. Bacterial adhesion was quantified by colony-forming unit (CFU) counting, and intracellular survival was assessed using a gentamicin protection assay. S. boulardii did not affect bacterial adhesion, but it significantly reduced intracellular ST survival, particularly under pretreatment conditions (p < 0.05). This effect was associated with increased iNOS gene expression. Interferon-γ expression was mainly induced by pretreatment, whereas tumor necrosis factor-α and interleukin-10 were modulated under cotreatment conditions. These findings indicate that S. boulardii modulates macrophage antimicrobial gene expression and suggest that probiotic pretreatment enhances innate immune responses against intracellular bacterial infections. Full article

Isoflurane is a widely used volatile anesthetic with context-dependent effects on neuronal survival, particularly in neurodegenerative conditions. Increasing evidence suggests that brief, sublethal stress exposure can induce adaptive cellular responses through hormesis-based preconditioning mechanisms. In this study, we investigated whether isoflurane preconditioning enhances neuronal tolerance to amyloid-β (Aβ)-induced toxicity and explored the underlying redox-dependent molecular pathways. Using HT-22 murine hippocampal neuronal cells, we demonstrate that short-term exposure to low-dose isoflurane induces a delayed neuroprotective phenotype characterized by improved cell viability, reduced apoptotic signaling, and maintained mitochondrial membrane potential following Aβ challenge. Mechanistically, isoflurane preconditioning elicited a mild and transient increase in intracellular reactive oxygen species (ROS), which is critical for the activation of the PI3K/Akt signaling pathway. Pharmacological scavenging of reactive oxygen species abolished Akt phosphorylation and reduced the protective effects of preconditioning, supporting a hormetic signaling model rather than direct antioxidant action. Following Akt activation, isoflurane preconditioning promoted the inhibitory phosphorylation of glycogen synthase kinase-3β (GSK-3β), decreased Keap1 protein levels, and facilitated nuclear translocation and transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Consequently, the expression of Nrf2-regulated antioxidant genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase 1 (NQO1), superoxide dismutase 1 and 2 (SOD1/2), and catalase, was significantly upregulated. Collectively, these findings indicate that isoflurane preconditioning confers neuroprotection through hormesis-like mild oxidative signaling and coordinated activation of endogenous antioxidant defenses rather than via direct antioxidant scavenging. Full article

Ewing sarcoma (ES) is the second most common primary bone malignancy in children and adolescents and remains one of the most lethal pediatric cancers. Found in more than 85% of patients with ES, EWSR1::FLI1 results from the t(11;22)(q24;q12) chromosomal translocation. This fusion encodes an aberrant transcription factor that dysregulates gene expression and drives oncogenic transformation. Although this oncogene was identified over three decades ago, therapeutic progress has been limited, in part due to the lack of robust and permissive animal models. Prior efforts to generate transgenic mouse models have been unsuccessful, and while zebrafish have emerged as a promising system, a tissue context capable of supporting EWSR1::FLI1-driven tumorigenesis has not been defined. Here, we report that tissue-specific expression of EWSR1::FLI1 in zebrafish induces tumor formation that recapitulates the histologic and molecular hallmarks of human ES, including small round blue cell morphology and characteristic biomarker expression. Tumors were driven by the col2a1a promoter and resulted in ~70% incidence of notochord tumors within the first 72–96 h. Of the surviving fish, ~5% developed CD99-positive small round blue cell tumors at ~9 months post-fertilization. This work establishes a stable tissue-specific transgenic model of ES, providing a powerful in vivo platform to investigate disease pathogenesis and evaluate novel therapeutic strategies. Full article

Background: Sulfate transporters (SULTRs) are integral membrane proteins responsible for sulfate uptake, translocation, and plant adaptation to abiotic stresses. However, knowledge regarding the SULTR gene family in the economically important crop, Brassica rapa (Chinese cabbage), limited. The aim of this study is to conduct a genome-wide identification and functional characterization of BrSULTR genes and to explore their potential functions under abiotic stress. Methods: We identified 19 BrSULTR genes in the B. rapa genome by performing homology searches with Arabidopsis thaliana SULTR sequences as queries. Subsequent bioinformatics analysis included phylogenetic classification, chromosomal localization, gene structure, conserved motif dissection, cis-regulatory element prediction, and protein–protein interaction (PPI) network analysis. Tissue-specific expression profiles of BrSULTRs were assessed using publicly available transcriptome data. Furthermore, their expression dynamics under salt (150 mM NaCl) and low-temperature (4 °C) stress were investigated by integrating transcriptomic, proteomic, and qRT-PCR data. Results: The 19 identified BrSULTR members were phylogenetically categorized into four subfamilies and were mapped unevenly across seven chromosomes. Promoter analysis identified an array of cis-regulatory elements associated with development, hormone response, and stress response. Expression profiles revealed distinct tissue-specific patterns in roots, stems, leaves, flowers, and siliques. Under salt stress, BrSULTR13 was significantly upregulated, while BrSULTR9 and BrSULTR11 were significantly suppressed under low-temperature stress. PPI network projection indicated that the Arabidopsis homologs of BrSULTR5 may physically interact with stress-regulating enzymes such as APS and APR. Conclusions: Our work presents a comprehensive genomic and functional overview of the BrSULTR gene family in B. rapa. The results underscore the potential functions of BrSULTRs, highlighting their involvement in sulfate transport and abiotic stress responses. These insights establish valuable insights and a foundation for further research aiming at improving stress tolerance in B. rapa through the manipulation of sulfur metabolism pathways. Full article

Contamination of agricultural soil by potentially toxic elements (PTEs) can be caused by volcanic emissions and the use of agrochemicals; this threatens human food security, as PTEs can be transferred from the soil to plant tissues. Sorghum is the fifth most important cereal crop worldwide, and Mexico is one of the countries with the highest sorghum production. However, these crops are vulnerable to pests; thus, agrochemicals are applied to eliminate them. In this study, the identification and translocation of PTEs into sorghum plants grown in urban and volcanic areas of central Mexico were evaluated. Sorghum plants and soil samples were collected at four sites (S1, S2, S3, and S4) in these areas. The concentrations of PTEs in the soil samples and in the different tissues of the sorghum plants were determined by inductively coupled plasma optical emission spectroscopy. It was found that these sites are contaminated with PTEs, which were attributed to volcanic emissions and anthropogenic activities. In addition, the translocation factor values for zinc, nickel, and manganese showed that these PTEs were retained in the roots of the sorghum plants; however, the average concentrations of these PTEs in the grains of the plants were higher than the translocation factor values. This result indicates that the aerial parts of the sorghum plants could have been contaminated with PTEs from the air, which could then enter humans throughout the food chain. Full article

The surrounding soil in mining areas generally suffers from severe pollution, characterized primarily by multi-metal contamination, and poses significant challenges in restoration and safe utilization. Therefore, it is urgent to explore low-cost restoration and safe utilization technologies that can achieve simultaneous treatment and utilization. This study selected a typical lead-zinc mining area in eastern Yunnan, China, where there is severe heavy metal pollution. It collected 15 common varieties of castor plants and systematically studied their absorption, accumulation, translocation, and removal characteristics of four heavy metal elements (Cd, Pb, Cu, Zn). The results showed that the heavy metal pollution in the mining area was extremely severe. Castor plants have a strong tolerance to heavy metal stress. There were significant differences in the absorption and accumulation of heavy metals among different castor varieties. The root parts mainly accumulated Pb, the stem parts mainly accumulated Cd, and the seeds had a higher ability to accumulate Cu. In terms of restoration potential, the Tong Castor No. 24, Fen Castor No. 10, and Zi Castor No. 3 plants had relatively large restoration potential. However, considering both biomass and heavy metal removal capacity, Dian Castor No, 2 Zi Castor No. 3, Dian Castor No. 5 plants were more ideal and could be applied in the restoration of heavy metal complex pollution soil in mining areas. Full article

Manganese (Mn) is an essential micronutrient required for plant growth, photosynthesis and metabolic regulation. Its importance is related to the involvement in several metabolic processes that ensure proper cellular function and balanced plant development throughout the production cycle. In plants, Mn is absorbed predominantly as Mn²⁺, and its availability is strongly influenced by soil pH, aeration, and other mineral nutrients in the soil solution. After uptake by roots, Mn is translocated to the shoot, accumulating primarily in metabolically active organs such as stems, young leaves and flowers. Although Mn exhibits limited mobility in the phloem, adequate concentrations are necessary to sustain both vegetative development and reproductive growth. Adequate Mn concentration is directly reflected in fruit development, as well-nourished plants show improved flowering, greater assimilate translocation capacity, and better fruit filling, thereby positively influencing yield and quality. However, Mn deficiency is common in alkaline soils or soils with high organic matter, causing interveinal chlorosis in young leaves, reduced growth, and lower biomass production. Under prolonged conditions, deficiency leads to less vigorous plants with reduced metabolic efficiency. Conversely, Mn toxicity, typically associated with acidic and poorly drained soils, restricts root development and induces nutritional imbalances with other elements, such as calcium, magnesium, and iron. Therefore, proper Mn management is essential to ensure nutritional balance and optimal performance of agricultural crops. Overall, this review synthesizes advances in Mn transport, cellular compartmentalization, and metabolic regulation, emphasizing how Mn interacts with other mineral nutrients to influence plant physiology. Attention is given to the integration of Mn with redox networks, photosynthetic regulation, and reproductive development. By linking transport mechanisms with physiological outcomes, this review identifies key patterns governing Mn homeostasis and highlights implications for crop nutrition and sustainable nutrient management. Full article

Renal ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury. Estradiol (E2) and the selective estrogen receptor modulator raloxifene (RAL) reduce organ dysfunction, potentially via heme oxygenase-1 (HO-1)–mediated antioxidant and anti-inflammatory effects. This study examined whether E2 and RAL protect against IRI through G protein-coupled estrogen receptor (GPER)–dependent activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 pathway in ovariectomized (OVX) mice; OVX IRI mice were pretreated for four weeks with E2, RAL, RAL + ML385 (Nrf2 inhibitor), or RAL + G15 (GPER antagonist). Renal histology, inflammatory and oxidative markers, and nuclear Nrf2 levels were assessed; OVX IRI increased interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA) and decreased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH); nuclear Nrf2 was low in sham and OVX IRI groups. E2 and RAL improved renal function and histology, reduced inflammation and oxidative stress, restored GPER expression, increased nuclear Nrf2, and upregulated HO-1 and NAD(P)H:quinone oxidoreductase 1 (NQO1). Co-treatment with ML385 or G15 reversed RAL’s benefits, reduced nuclear Nrf2, and worsened injury; E2 and RAL exert renoprotective effects against OVX-related renal IRI in a manner consistent with GPER-dependent Nrf2 nuclear translocation, which suggests involvement of the downstream antioxidant gene activation pathway. Full article

Epiphytic lichens are highly sensitive components of forest ecosystems, increasingly threatened by habitat disturbance and climate change. While habitat protection remains central to lichen conservation, translocation has emerged as a promising tool to address population decline, although its global effectiveness remains poorly evaluated. This scoping review, conducted under PRISMA-ScR guidelines, analyzes 30 taxa across 12 countries to evaluate current methodologies and outcomes. The reviewed literature is largely characterized by small-scale, method-oriented interventions, with a strong predominance of thallus fragment translocation over diaspore-based approaches. Success is most often evaluated through short-term survival and persistence of transplanted material, whereas indicators of long-term population self-maintenance and reproductive viability are rarely considered. Major limitations emerge from technical constraints, including early sample loss due to inadequate fixation, as well as from mismatches between donor requirements and recipient-site microhabitat conditions. Although high initial survival is frequently reported, evidence for long-term population stability, secondary colonization, and genetic resilience remains scarce. Overall, translocation may support short-term establishment under favorable environmental conditions, mainly at local scales, but its reliability as a long-term conservation strategy requires further validation. This review identifies a critical gap in long-term monitoring and highlights the need for research priorities that enhance the effectiveness, conceptual clarity, and technical precision of future translocation efforts to ensure the persistence of epiphytic lichen populations within changing forest landscapes. Full article

Background and Clinical Significance: Burkitt lymphoma is an aggressive form of non-Hodgkin lymphoma of B-cell origin, caused by a MYC gene translocation on chromosome 8. There are three clinical subtypes, of which the sporadic subtype is most prevalent in the United States. Sporadic Burkitt lymphoma is diagnosed at a median age of 30 years and commonly manifests as bulky abdominal lesions, most often involving the ileocecal region. Pancreatic involvement is uncommon, and presentation as acute pancreatitis secondary to Burkitt lymphoma is exceedingly rare. Case Presentation: We present a case of a young male who presented with epigastric pain, nausea, and vomiting. He had a diffusely tender abdomen and elevated lipase levels. On imaging, he was found to have large retroperitoneal and intraperitoneal masses, contiguous with an enlarged pancreas. Burkitt lymphoma was confirmed upon biopsy of duodenal and gastric masses via endoscopic ultrasound. MRI brain and testicular ultrasound revealed unilateral fifth cranial nerve and bilateral testicular involvement, respectively. His course was complicated by bowel perforation requiring urgent surgery. However, he achieved complete remission with dose-dense systemic and intrathecal chemotherapy. Conclusions: This case highlights the diverse presentations of Burkitt’s lymphoma and a favorable prognosis with treatment. Clinicians should maintain a high index of suspicion for a malignant etiology of acute pancreatitis in patients without classic risk factors. Full article

Escherichia coli, Streptococcus equi subsp. zooepidemicus, Klebsiella oxytoca, and Enterococcus durans are microorganisms capable of causing severe infections, particularly in patients with underlying comorbidities or immune dysfunction. We report a rare clinical case of a 65-year-old man with advanced cardiac and hepatic disease who developed severe diarrheal syndrome followed by septic shock, rapid clinical deterioration, and death. Microbiological examination of autopsy specimens from the intestinal wall and spleen identified Escherichia coli O128 with an enterotoxigenic profile (lt+, st+, eae−), together with Streptococcus equi subsp. zooepidemicus, Klebsiella oxytoca, and Enterococcus durans. Histopathological analysis demonstrated catarrhal enteritis with fibrinous deposits, mucosal edema, vascular congestion, and inflammatory infiltration. Although the microbiological findings were partly derived from autopsy material and postmortem bacterial translocation cannot be completely excluded, the concordance between clinical presentation, laboratory findings, and morphological changes supports the presence of a clinically significant infectious process. To our knowledge, this is the first reported human case of fatal polymicrobial infection involving these four pathogens. The case highlights the potential severity of polymicrobial infections in patients with cirrhosis-associated immune dysfunction and underscores the importance of integrated microbiological and molecular diagnostics for accurate etiological assessment. Full article

The mitochondrial anti-viral signaling protein, MAVS, is a central regulator of innate anti-viral immunity. Recently, we demonstrated that MAVS is overexpressed in cancer, where its downregulation resulted in reduced cell proliferation and the expression and nuclear translocation of proteins associated with transcriptional regulation and inflammation. In this study, we demonstrate that CRISPR/Cas9-mediated MAVS depletion in PC-3 prostate cancer cells suppresses proliferation, disrupts immune evasion, and alters the tumor microenvironment. Proteomic profiling of the MAVS-KO cells by LC-MS/MS revealed changes in the expression of proteins associated with immunity, cell signaling, mitochondrial function, metabolism, protein synthesis and degradation, and epigenetic regulation. In contrast to MAVS-expressing cells, MAVS-KO cells implanted subcutaneously in mice formed very small tumors. This inhibited tumor growth was linked to reduced proliferation, and enhanced apoptosis, as indicated by strong TUNEL staining and elevated activated caspase-3. Importantly, the small “tumors” derived from MAVS-KO cells displayed a distinct morphology: diminished cancer stem-cell populations, an altered tumor microenvironment and inflammatory response, increased immune cell infiltration, and reduced PD-L1 expression. Together, these findings establish MAVS as a key mediator of cancer-cell survival, inflammation, and immune regulation, and, thus, its upregulation in tumors makes it a potential anti-cancer target. Full article

Cadmium (Cd) contamination of agricultural soils poses a serious threat to crop productivity and food safety due to its high mobility, bioaccumulation potential, and toxicity. This study investigated the effects of increasing Cd levels on growth performance, physiological responses, Cd partitioning, mineral nutrient disruption, and Cd accumulation in four Brassicaceae crops (cress, watercress, broccoli, and white cabbage). Plants were grown in plastic pots filled with 4 kg of soil under controlled greenhouse conditions and exposed to five different Cd concentrations (0, 5, 10, 20, and 50 mg kg⁻¹). Cd exposure significantly affected growth and physiological responses in a species-dependent manner. Compared to the control, shoot dry weight decreased by up to 66.4% in broccoli and 51.7% in cress at the highest Cd level, while white cabbage exhibited comparatively greater tolerance. Oxidative stress indicators showed contrasting patterns, with hydrogen peroxide (H₂O₂) increasing by up to 8.8-fold, whereas proline and membrane permeability (MP) responses varied among species. Photosynthetic pigments declined in cress but increased in broccoli under high Cd conditions, suggesting differential adaptive strategies. Cd accumulated predominantly in roots; however, root retention capacity declined at elevated Cd concentrations (20–50 mg kg⁻¹ soil), leading to greater Cd translocation to shoots. Elevated translocation factors and shoot Cd distribution demonstrated that physiological tolerance did not necessarily limit Cd accumulation in edible tissues. Cd stress also induced notable imbalances in essential mineral nutrients, particularly potassium (K), calcium (Ca), and zinc (Zn), reflecting strong Cd–nutrient interactions at uptake and transport levels. These nutrient disruptions not only exacerbated physiological stress responses but also reduced the nutritional quality of plant tissues. Notably, species maintaining relatively stable growth under moderate Cd exposure still accumulated substantial Cd concentrations in shoots, highlighting a critical disconnect between agronomic performance and food safety. In conclusion, the findings demonstrate that Brassicaceae crops exhibit contrasting strategies in response to Cd stress, with significant implications for Cd entry into the food chain. The study emphasizes the importance of integrating physiological assessment with metal partitioning and nutrient balance analyses when evaluating crop suitability for cultivation in Cd-contaminated soils and for mitigating potential risks to human health. Full article

Complex I (NADH:quinone oxidoreductase, CI) is central to cellular aerobic energy metabolism. The L-shaped structure of CI is unique, where the hydrophilic arm is responsible for the electron transfer function and the membrane arm operates proton pumping. These two functional sites are spatially far apart yet functionally connected. This basic core subunit architecture is highly conserved from bacterial to mammalian CI. Here, to gain detailed mechanistic insight into the role of the membrane subunit ND2 in the coupling mechanism, we mutated several highly conserved residues in the middle of the membrane axis of NuoN, the E. coli CI homolog of ND2. To more precisely investigate the consequences of mutational effects on highly conserved residues, we purified each mutant CI and compared the mutational effects on electron transfer and proton pumping activity using our instant membrane reconstitution method with E. coli double knockout (DKO) membrane vesicles lacking both CI and alternative NADH dehydrogenase (NDH-2). Thre results were corroborated by conventional proteoliposome reconstitution experiments. We found that Lys247 and Lys395 are absolutely essential for both electron transfer and proton pumping activities, while about 50% reduction of NADH oxidase activity but no reduction in proton pumping activity was observed in Lys217, and no significant decrease was detected in Glu133. Furthermore, unexpectedly, we were able to purify an NuoN knockout (ΔNuoN) mutant, which contained stoichiometric peripheral subunits NuoB, NuoCD, NuoE, NuoF, NuoG, and NuoI; and a substoichiometric amount of NuoH and a reduced amount of quinone. However, surprisingly, this isolated ΔNuoN CI showed CI activities (~30% of the WT) after being reconstituted into DKO membranes but not into proteoliposomes. Later, we confirmed by blue native PAGE that the wild-type CI was partially formed from ΔNuoN CI by recruiting its missing membrane subunits that existed in DKO membranes. Our data strongly suggest that ND2/NuoN plays an essential role in the coupling mechanism in CI. CI is the entry respiratory chain enzyme and is central to cellular energy metabolism. Two highly conserved lysine residues in the center of the antiporter-like membrane subunit ND2 are essential for the coupling mechanism between electron transfer and proton translocation. Full article

Climate change is radically altering the Earth’s natural ecosystems, with temperature/precipitation alterations resulting in mismatches between specific ecosystems and their ‘new’ climatic profiles. Without political action to curb greenhouse gas emissions, most plant/animal species will need to move to higher latitudes to ensure survival. Many are incapable of migrating rapidly and will thus be reliant on human intervention to relocate to new regions (assisted migration). The first hypothetical steps of assisted migration are explored here, using the UK as a model. Urban parks/gardens have a history of hosting non-native plant species and could be used to test the validity of moving non-native plants and animals to regions of higher latitude. In this perspective paper, we added a small experimental component to examine public attitudes to species introductions into urban parks/gardens. Results showed support for using parks and gardens to protect both UK native and non-native wildlife. Indeed, >50% of respondents favoured utilising urban landscapes to conserve small non-native animals (e.g., tortoises and bee-eaters). These results imply there may be some public acceptance of assisted migration. Thus, the paper explores the potential to develop novel, but more sustainable ecosystems in new localities. Full article