Search Results (33,719)

Background/Objectives: Hippocampal neuroinflammation (HNF) is a key pathological feature in neurodegenerative disorders. Milk-derived exosomes, as bioactive extracellular vesicles, have underexplored potential in regulating brain neuroinflammatory responses. This study aimed to characterize desert milk exosomes (D-Exo) and investigate their neuroprotective and anti-neuroinflammatory effects in LPS-induced HNF mice model and an LPS-stimulated BV2 microglia. Methods: Exosomes were isolated from desert and non-desert milk (ND-Exo) for proteomic analysis. After pretreating BV2 cells with exosomes and stimulating with LPS, their inflammatory responses and polarization were assessed by RT-PCR. Balb/c mice were orally gavaged with D-Exo or 0.9% NaCl for 28 days before LPS injection. Cognitive function was assessed via behavioral tests, with microglial/astrocyte activation analyzed by immunofluorescence. Results: D-Exo exhibited superior stability and a unique proteomic profile enriched with proteins linked to neuroinflammation and blood-brain barrier (BBB) integrity, notably within the AMPK signaling pathway. In vitro, D-Exo shifted LPS-stimulated microglia from the M1 to the M2 phenotype. In vivo, it alleviated HNF and cognitive decline, reduced Aβ_1-42 and Tau deposition, elevated BDNF and MAP2, and suppressed neuroinflammation and glial activation. Conclusions: D-Exo is enriched with specific proteins, attenuates neuroinflammation and cognitive decline by regulating microglial M1/M2 polarization and AMPK pathway, highlighting its preventive potential. Full article

Tax evasion is a dynamic process reflecting continuous interaction between taxpayers and regulatory institutions rather than a static deviation from fiscal equilibrium. This study introduces a predator-prey model of tax evasion that translates the Lotka-Volterra framework from biology into budgetary dynamics. The model captures the feedback between the volume of tax evasion and the intensity of regulation, incorporating nonlinearity, implicit reactive lag, and adaptive response. Theoretical derivation and numerical simulation identify three dynamic regimes—stable equilibrium, limit-cycle oscillation, and instability—that arise through a Hopf bifurcation. Bifurcation maps in the (r, a), (r, b), and (r, c) parameter spaces reveal how control efficiency, institutional inertia, and behavioral feedback jointly determine fiscal stability. Results show that excessive enforcement may destabilize the system by inducing regulatory fatigue, while weak control enables exponential growth in evasion. The model provides a dynamic analytical tool for evaluating fiscal policy efficiency and identifying stability thresholds. Its findings suggest that adaptive, feedback-based regulation is essential for maintaining long-term tax discipline. The study contributes to closing the research gap by providing a unified dynamic framework linking micro-behavioral decision-making with macro-fiscal stability, offering a foundation for future empirical calibration and behavioral extensions of fiscal systems. Full article

Salinity stress severely constrains plant growth and ecosystem functioning in arid and semi-arid regions, and plant growth-promoting rhizobacteria (PGPR) have been increasingly applied to enhance plant salt tolerance. Hoswever, it remains unclear whether different PGPR inoculation strategies confer salt resistance through similar or distinct physiological pathways, particularly in perennial halophytes adapted to saline environments. In this study, a field experiment was conducted to evaluate the effects of single- and multi-strain PGPR inoculation on the growth performance, physiological responses, and stress regulation of Atriplex canescens under saline conditions. Plant biomass allocation, photosynthetic traits, osmotic adjustment substances, antioxidant enzyme activities, and comprehensive stress tolerance indices were systematically assessed. The results showed that PGPR inoculation significantly improved plant growth and stress tolerance; however, the magnitude and underlying mechanisms varied across inoculation strategies. Single-strain inoculation predominantly enhanced root development and antioxidant regulation, whereas multi-strain inoculation tended to promote aboveground growth and photosynthetic performance. In contrast, certain strain combinations did not produce additive benefits, suggesting potential incompatibility among microbial consortia under salt stress. Multivariate analyses further indicated that improvements in stress tolerance were more closely associated with coordinated physiological regulation than with biomass accumulation alone. Overall, our findings demonstrate that PGPR-mediated salt tolerance in A. canescens is strategy-dependent and involves distinct resource allocation and stress-defense pathways. These results highlight the importance of considering inoculation strategies and functional compatibility when applying PGPR to improve plant performance in saline ecosystems. Full article

Tomato (Solanum lycopersicum L.) is an important horticultural crop. Carotenoid cyclase dioxygenase (CCD) is an enzyme responsible for cleaving carotenoids, which is involved in regulating plant growth and response to abiotic stresses. However, the role of SlCCDs in tomato stress resistance remains unclear. This study used the tomato variety ‘Micro-Tom’ as the material to investigate the function of SlCCDs in stress responses. Through whole-genome analysis, a total of 12 SlCCDs members (SlCCD1–SlCCD12) were identified. Systematic evolutionary analysis classified them into four branches, and members within the same branch maintained a conserved structure. The promoter analysis revealed that SlCCDs contain multiple hormones and stress response elements. The qRT-PCR analysis revealed that SlCCD11 was the most highly expressed gene in the leaves. In addition, multiple SlCCDs showed significant responses to abscisic acid (ABA), methyl jasmonate (MeJA), light, and sodium chloride (NaCl) treatments. Among them, the expression of SlCCD11 significantly increased under salt stress. By silencing SlCCD11 using virus-induced gene silencing (VIGS) technology, it was found that the chlorophyll content, antioxidant enzyme activity, and ABA-related gene expression in the TRV:SlCCD11 plants under salt stress were all lower than the control samples, while the carotenoid content and ROS accumulation were higher. This indicates that SlCCD11 is a positive regulatory factor for salt stress. In conclusion, this study systematically analyzed the SlCCD gene family and revealed the positive role of SlCCD11 in tomato response to salt stress, providing a candidate gene for genetic improvement of crop stress resistance. Full article

Cancer stem cells (CSCs) represent a small but highly resilient tumor subpopulation responsible for sustained growth, metastasis, therapeutic resistance, and recurrence. Their survival is supported by aberrant activation of developmental and inflammatory pathways, including Wnt/β-catenin, Notch, Hedgehog, PI3K/Akt/mTOR, STAT3, and NF-κB, as well as epithelial–mesenchymal transition (EMT) programs and niche-driven cues. Increasing evidence shows that phytochemicals, naturally occurring bioactive compounds from medicinal plants, can disrupt these networks through multi-targeted mechanisms. This review synthesizes current findings on prominent phytochemicals such as curcumin, sulforaphane, resveratrol, EGCG, genistein, quercetin, parthenolide, berberine, and withaferin A. Collectively, these compounds suppress CSC self-renewal, reduce sphere-forming capacity, diminish ALDH⁺ and CD44⁺/CD24⁻ fractions, reverse EMT features, and interfere with key transcriptional regulators that maintain stemness. Many phytochemicals also sensitize CSCs to chemotherapeutic agents by downregulating drug-efflux transporters (e.g., ABCB1, ABCG2) and lowering survival thresholds, resulting in enhanced apoptosis and reduced tumor-initiating potential. This review further highlights the translational challenges associated with poor solubility, rapid metabolism, and limited bioavailability of free phytochemicals. Emerging nanotechnology-based delivery systems, including polymeric nanoparticles, lipid carriers, hybrid nanocapsules, and ligand-targeted formulations, show promise in improving stability, tumor accumulation, and CSC-specific targeting. These nanoformulations consistently enhance intracellular uptake and amplify anti-CSC effects in preclinical models. Overall, the consolidated evidence supports phytochemicals as potent modulators of CSC biology and underscores the need for optimized delivery strategies and evidence-based combination regimens to achieve meaningful clinical benefit. Full article

The interlayer is a key geological factor that regulates reservoir heterogeneity and remaining oil distribution, and its accurate identification directly affects the reservoir development effect. To address the strong subjectivity of traditional identification methods and the insufficient recognition accuracy of single machine learning models under imbalanced sample distributions, this study focuses on three types of interlayers (argillaceous, calcareous, and petrophysical interlayers) in the W Oilfield, and proposes an accurate identification method integrating the Synthetic Minority Over-Sampling Technique (SMOTE) and heterogeneous ensemble learning. Firstly, the corresponding data set of interlayer type and logging response is established. After eliminating the influence of dimension using normalization, the sensitive logging curves are optimized using the crossplot method, mutual information, and effect analysis. SMOTE technology is used to balance the sample distribution and solve the problem of the identification deviation of minority interlayers. Then, a heterogeneous ensemble model composed of the k-nearest neighbor algorithm (KNN), decision tree (DT), and support vector machine (SVM) is constructed, and the final recognition result is output using a voting strategy. The experiments show that SMOTE technology improves the average accuracy of a single model by 3.9% and effectively improves the model bias caused by sample imbalance. The heterogeneous integration model improves the overall recognition accuracy to 92.6%, significantly enhances the ability to distinguish argillaceous and petrophysical interlayers, and optimizes the F1-Score simultaneously. This method features a high accuracy and reliable performance, providing robust support for interlayer identification in reservoir geological modeling and remaining oil potential tapping, and demonstrating prominent practical application value. Full article

This paper proposes E-MOTE (Emotion-aware Teacher Education Framework), an ethically grounded conceptual model aimed at enhancing teacher education through the integrated use of the Facial Action Coding System (FACS), Artificial Intelligence (AI), and Virtual Reality (VR). As a conceptual and design-oriented proposal, E-MOTE is presented as a structured blueprint for future development and empirical validation, not as an implemented or evaluated system. Grounded in neuroscientific and educational research, E-MOTE seeks to strengthen teachers’ emotional awareness, teacher noticing, and social–emotional learning competencies. Rather than reporting empirical findings, this article offers a theoretically structured framework and an operational blueprint for the design of emotion-aware teacher training environments, establishing a structured foundation for future empirical validation. E-MOTE articulates three core contributions: (1) it clarifies the multi-layered construct of emotion-aware teaching by distinguishing between emotion detection, perception, awareness, and regulation; (2) it proposes an integrated AI–FACS–VR architecture for real-time and post hoc feedback on teachers’ perceptual performance; and (3) it outlines a staged experimental blueprint for future empirical validation under ethically governed conditions. As a design-oriented proposal, E-MOTE provides a structured foundation for cultivating emotionally responsive pedagogy and inclusive classroom management, supporting the development of perceptual micro-skills in teacher practice. Its distinctive contribution lies in proposing a shift from predominantly macro-behavioral simulation toward the deliberate cultivation of perceptual micro-skills through FACS-informed analytics integrated with AI-driven simulations. Full article

Pathogenic bacteria utilize a type III secretion system (T3SS) to inject type III effectors (T3Es) into plant cells, suppressing plant immunity and facilitating colonization. Paracidovorax citrulli, the causal agent of bacterial fruit blotch (BFB) of Cucurbitaceae crops, harbors a functional T3SS like many other plant pathogens. The expression of its T3SS and T3Es is regulated by the two-component system response regulators HrpG and HrpX. Here, we demonstrate that the aspartic acid (Asp) residues at positions 52 and 60 in P. citrulli HrpG are essential for its complete function. Plasmid-mediated complementation of the ΔhrpG mutant with hrpG carrying Asp52→alanine (Ala) or Asp60→Ala mutations failed to restore the ability of P. citrulli to induce a hypersensitive response (HR) in tobacco, whereas the Asp46→Ala mutation fully rescued this phenotype. Furthermore, genomic hrpG point mutations generating strains Aac5 (D52A) and Aac5 (D60A) abolish the activation of hrpX transcription, resulting in decreased HrpX accumulation. Collectively, Asp 52 and Asp 60 in P. citrulli HrpG are essential for transcriptional activation activity of hrpX and HR induction, serving as a potential phosphorylation site (Asp 52) for upstream histidine kinases and a Mg²⁺ coordination site (Asp 60). Given that conserved Asp residues often function as phosphorylation sites in two-component system response regulators, this study provides a foundation for identifying upstream histidine kinases that modulate HrpG activity in P. citrulli. Full article

Multipotent mesenchymal stromal stem cells have captivated the scientific community in recent years due to their ability to differentiate into multiple adult cell types. Central to this potential are many members of the nuclear hormone receptor superfamily, comprising 48 ligand-modulated transcription factors involved in key biological processes such as metabolism, physiology, embryonic development, and reproduction. These transcription factors influence cellular fate by regulating gene expression networks critical for MSC specification, commitment, and differentiation. This review explores the role of nuclear receptors in MSC development, focusing on interactions with chromatin structure, co-regulatory complexes, and responsiveness to extracellular stimuli such as hormones, metabolic cues, and endocrine-disrupting chemicals. We conclude with a discussion of the dangers posed by exogenous and aberrant signaling through nuclear receptors. Full article

L-ascorbic acid (ASA) is an essential micronutrient critical for antioxidant defense and metabolic regulation in animals. Unlike many vertebrates, Drosophila melanogaster possesses the ability to synthesize ASA endogenously, yet the regulatory mechanisms governing this biosynthesis remain unclear. 2-keto-L-gulonic acid (2KGA), a key precursor in industrial vitamin C production, has been shown to enhance ASA accumulation in plants, but its role in invertebrates is unknown. This study systematically investigated the effect of exogenous 2KGA supplementation on ASA biosynthesis in Drosophila. Fruit flies were reared on media with or without 2KGA (1.6 g/L; n = 30 per group) for 12 days, followed by ASA quantification via high-performance liquid chromatography (HPLC). Results showed that 2KGA treatment increased mean ASA content from 0.00853 ± 0.0012 to 0.01064 ± 0.0015 μg/fly (24.74% increase; p = 0.0194, r² = 0.558) compared to the control group, indicating that 2KGA acts as a metabolic regulator to promote ASA biosynthesis. Sex-separated analyses further revealed that this effect was primarily driven by male flies (p = 0.0057, r² = 0.879), whereas females showed no significant response (p = 0.1783), pointing to a sex-dependent regulation of 2KGA-mediated ASA biosynthesis. These findings provide the first evidence that 2KGA modulates ASA levels in an invertebrate disease model and suggest that fruit flies can serve as a useful platform to explore conserved redox-regulatory mechanisms relevant to human health and disease. Full article

Squamosa promoter binding protein (SBP) plays a vital role in plant growth, development, and responses to abiotic stresses. The genus Notopterygium is an endangered perennial herbaceous plant mainly distributed in the high-altitude Qinghai–Tibet Plateau and adjacent areas, which possibly occurred the adaptive evolution to the extreme environmental conditions. In this study, we firstly determined the genome-wide structural characteristics, evolutionary history, and expression profiles of the SBP family genes in Notopterygium species by using genome, transcriptome, and DNA resequencing data. We have also investigated the response patterns of SBPs of N. franchetii to the drought and high-temperature stresses. The 21, 18, and 18 SBP family genes of three Notopterygium species, N. incisum, N. franchetii, and N. forrestii, were, respectively, identified and classified into eight subfamilies, with four subfamily members regulated by miR156. The structure analysis showed that the members of the same SBP subfamily had similar structures and conserved motif composition. Cis-element analysis suggested that those SBP genes may have been essential to the growth and environmental adaptation of Notopterygium. The expansion of the SBP gene family was mainly caused by the whole genome duplication/segmental duplication and transposable element duplication. Evolutionary analysis showed the SBP gene family experienced severe contraction events and most of the gene copies underwent purification selection. Population genetics analysis based on SBPs variations suggested that the genus Notopterygium species have obvious genetic structure and interspecific differentiation. RNA-seq and qRT-PCR experiments demonstrated that the expressions of SBPs genes in Notopterygium were not species-specific, but tissue-specific. NinSBP08 and NinSBP10/12 may have played the key roles in heat tolerance and drought resistance, respectively. These results provided novel insights into the evolutionary history of the SBP gene family in the endangered herb Notopterygium species in the high-altitude Qinghai–Tibet Plateau and adjacent areas. Full article

Hyperphosphorylated collapsin response mediator protein 2 (CRMP2) is elevated in the cerebral cortex of an APP-SAA knock-in mouse model of Alzheimer’s disease and binds the adenine nucleotide translocase (ANT) in a phosphorylation-dependent manner. We propose that, in Alzheimer’s disease (AD) mitochondria, dissociation of hyperphosphorylated CRMP2 from ANT promotes opening of the permeability transition pore (PTP). We showed that purified ANT, when reconstituted into giant liposomes, forms large calcium-dependent channels resembling the PTP, which are effectively blocked by recombinant, unphosphorylated CRMP2. In synaptic mitochondria isolated from the cortices of APP-SAA knock-in mice and control B6J hAbeta mice, we observed an increased susceptibility to permeability transition pore (PTP) induction in AD mitochondria, accompanied by reduced viability of cultured cortical neurons. Pre-treatment of AD mice with the CRMP2-binding small molecule (S)-lacosamide ((S)-LCM), which prevents CRMP2 hyperphosphorylation and restores its interaction with ANT, attenuated PTP induction and improved neuronal viability. Interestingly, direct application of (S)-LCM to isolated mitochondria failed to suppress PTP induction, indicating that its protective effect requires upstream cellular mechanisms. These findings support a phosphorylation-dependent role for CRMP2 in regulating PTP induction in AD mitochondria and highlight (S)-LCM as a promising therapeutic candidate for mitigating mitochondrial dysfunction and enhancing neuronal viability in AD. Full article

Background: Persistent liver pathology despite a sustained virologic response (SVR) to hepatitis C virus (HCV) therapy is a major clinical concern. This is particularly relevant for people with HIV (PWH) with HCV coinfection, a population prone to accelerated liver disease progression. This study aimed to characterize the plasma miRNA profile in PWH with cirrhosis one year after successful completion of HCV therapy, and to explore their relationship with metabolite alterations. Methods: This cross-sectional study enrolled 47 PWH who achieved HCV clearance with antiviral therapy. Using plasma samples collected approximately one year after completion of HCV therapy, participants were stratified into two groups based on liver stiffness measurement (LSM): compensated cirrhosis (n = 32, LSM ≥ 12.5 kPa) and non-cirrhosis (n = 15, LSM < 12.5 kPa). Plasma miRNAs and metabolites were determined using small RNA sequencing and untargeted capillary electrophoresis-mass spectrometry (CE-MS), respectively. Significantly differentially expressed (SDE) miRNAs were identified using generalized linear models (GLM) with a negative binomial distribution, and their correlation with metabolite levels was quantified using Spearman’s correlation. Results: In the cirrhosis group (n = 32), we identified a distinct signature of 15 SDE miRNAs (9 upregulated, 6 downregulated) compared to the non-cirrhotic group (n = 15), showing hsa-miR-10401-3p, hsa-miR-548ak, hsa-miR-141-3p, and hsa-miR-3940-3p the largest expression changes. miRNA-gene interaction and pathway enrichment analysis suggested that these 15 SDE miRNAs potentially regulate multiple genes involved in immune response and amino acid metabolism. In addition, correlation analyses with our metabolomic data revealed significant associations between specific SDE miRNAs and amino acids and their derivatives. Specifically, the expression of upregulated miRNAs (e.g., hsa-miR-10401-3p and hsa-miR-16-5p) was positively correlated with plasma levels of L-methionine and its derivatives, while downregulated miRNAs (e.g., hsa-miR-625-5p) were inversely correlated with L-tryptophan. Conclusions: In cirrhotic PWH with history of HCV coinfection, a distinct plasma miRNA signature linked to dysregulated amino acid metabolism is found one year after completion of HCV therapy. This underscores that the HCV cure does not equate to complete hepatic recovery, highlighting the critical need for long-term monitoring in this high-risk population. Full article

The increasing accumulation of plastic debris in aquatic environments has raised concerns about the ecotoxicological effects of polystyrene nanoplastics (PSNPs). This study examined PSNPs toxicity during a critical developmental stage by exposing 15 days post-fertilization (dpf) larvae of blotched snakehead (Channa maculata), an economically important freshwater fish, to PSNPs concentrations of 0.05–20 mg/L for 15 days. Histopathological analysis showed concentration-dependent damage, including hepatocellular vacuolization (5–10 mg/L) and hepatic sinusoidal dilation (20 mg/L) in the liver, alongside intestinal injuries ranging from villus erosion to rupture (5–20 mg/L). Biochemically, PSNPs triggered a biphasic oxidative response, where superoxide dismutase (SOD) and catalase (CAT) activities peaked at 5 mg/L before declining, while malondialdehyde (MDA) levels exhibited an opposite trend. Transcriptomic analysis and Quantitative real-time PCR (qRT-PCR) indicated that PSNPs disrupted growth, energy metabolism, and immune regulation in C. maculata larvae, evidenced by the dysregulation of growth hormone/insulin-like growth factor (GH/IGF) axis genes and up-regulation of immune-related genes. Furthermore, Weighted Gene Co-expression Network Analysis (WGCNA) identified the heterogeneous nuclear ribonucleoproteins (HNRNP) gene family as hub genes from the key turquoise module, suggesting that PSNPs interfere with RNA processing and post-transcriptional control. In summary, PSNPs caused multi-level toxicity in C. maculata larvae, providing new insights into their ecotoxicological hazards in freshwater ecosystems. Full article

Cadmium (Cd) drastically inhibits plant growth and metabolism, whereas arbuscular mycorrhizal (AM) fungi can enhance plant Cd tolerance through metabolic regulation. To clarify tissue-specific responses, we conducted a pot experiment combined with GC-MS to examine how AM fungi influence root and leaf metabolism of ryegrass (Lolium perenne L.) under different Cd levels. Root and leaf metabolomes diverged substantially in composition and function. In total, 83 metabolites were identified in roots, mainly phenolics, amines, and sugars associated with carbon–nitrogen metabolism and stress-defense pathways, whereas 75 metabolites were identified in leaves, largely related to photosynthetic metabolism. Roots were more sensitive to Cd, showing significant metabolic alterations at Cd ≥ 5 mg·kg⁻¹, including disruption of galactose metabolism, while leaves exhibited notable changes only at Cd ≥ 100 mg·kg⁻¹, with suppression of citrate, L-aspartate, and starch and sucrose metabolism. AM fungi modulated plant metabolism more strongly under Cd stress. Specifically, AM fungi restored Cd-suppressed galactose and glyoxylate/dicarboxylate metabolism in roots, enhanced starch and sucrose metabolism and amino acid pathways in leaves, and increased stress-related amino acids and organic acids in both tissues. Overall, AM fungi substantially alleviated Cd-induced metabolic inhibition, particularly at Cd ≥ 50 mg·kg⁻¹, providing mechanistic insight into AM-enhanced Cd tolerance and supporting the application of AM symbiosis in remediation of Cd-contaminated soils. Full article