Search Results (1,689)

Bovine viral diarrhea virus (BVDV), a significant global pathogen threatening cattle industries worldwide, presents substantial challenges for disease control. Its ability to infect cattle across all age groups, coupled with incompletely understood transmission mechanisms, complicates prevention and treatment strategies. We previously reported that BVDV induced tunneling nanotubes (TNTs)—F-actin-rich cytoplasmic connections between adjacent cells—and utilizes these structures for intercellular transmission. In this study, we used lentiviral transfection to express various structural and non-structural proteins of BVDV and identified NS5A as a critical viral protein that induces the formation of TNTs. RNA-seq analysis revealed that CKAP2, a host protein, plays a key role in TNT generation, with the PI3K/AKT/mTOR signaling pathway being essential for this process. Further investigation demonstrated that CKAP2 interacts with BVDV NS5A, triggering the activation of the PI3K/AKT/mTOR pathway, thereby promoting TNT formation and enhancing viral dissemination. Our data highlight a previously unknown mechanism of BVDV spreading and replication, which could have significant implications for within-host spread and immune evasion. Full article

Background: Prostate cancer (PCa) is the most commonly diagnosed malignancy in men and a leading cause of cancer-related mortality worldwide. Growing evidence indicates that metabolic syndrome components, including obesity, insulin resistance, and hyperglycemia, contribute to PCa development, and progression to more aggressive form. At the same time, standard treatments such as androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs) significantly improve oncologic outcomes but are associated with adverse metabolic effects, including increased fat mass, insulin resistance, and sarcopenia, potentially worsening patients’ overall metabolic profile and quality of life. Tumor progression in PCa is strongly driven by androgen receptor (AR) signaling, which is closely linked to cellular metabolic reprogramming, highlighting metabolism as a potential therapeutic target. Aim: The aim of this study was to evaluate and synthesize current evidence on the role of the ketogenic diet (KD) in PCa, with particular emphasis on its interaction with hormonal therapies, underlying metabolic and endocrine mechanisms, and its potential application as an adjunctive strategy in integrated oncologic care. Results: The KD, characterized by high fat and very low carbohydrate intake, induces a metabolic state of ketosis that reduces circulating glucose, insulin, and insulin-like growth factor 1 (IGF-1), potentially counteracting metabolic alterations associated with PCa and its treatments. Preclinical studies consistently demonstrate that carbohydrate restriction and KD can slow tumor growth, modulate key oncogenic pathways such as PI3K/AKT/mTOR, reduce systemic insulin signaling, and enhance survival in prostate cancer models. Additionally, emerging evidence suggests possible synergistic effects when KD is combined with standard therapies, including ADT and immunotherapy. Clinical data, although limited, indicate that low-carbohydrate dietary interventions may improve metabolic parameters and could delay biochemical progression, as suggested by increased prostate-specific antigen (PSA) doubling time. However, results across studies remain heterogeneous, and robust evidence on long-term oncologic outcomes is lacking. Conclusions: Overall, the KD represents a promising but still experimental strategy in PCa management, requiring careful nutritional supervision to avoid adverse effects such as unintended weight loss or sarcopenia. Further well-designed randomized clinical trials are needed to clarify its safety, efficacy, and role in routine clinical practice. Full article

This study aimed to identify candidate molecular pathways mediating dopaminergic dysfunction induced by PFAS mixture exposure, with a focus on the TM/5-HT signaling axis and calcium-linked lipid metabolites, and to explore potential gut-brain axis involvement. Adult mice were exposed to a PFAS mixture. Behavioral tests assessed spatial memory, spontaneous activity, and motor coordination. Histopathological and ultrastructural analyses examined neuronal atrophy, mitochondrial damage, α-synuclein (α-syn), and tyrosine hydroxylase (TH). Transcriptomics, metabolomics, and gut microbiota profiling (16S rRNA sequencing) were performed, followed by integrated multi-omics and correlation analyses. PFAS exposure was associated with PD-relevant motor and cognitive impairments, including impaired spatial memory, reduced spontaneous activity, and motor coordination deficits. Neuronal atrophy, mitochondrial structural damage, upregulation of α-syn, and downregulation of TH were observed. Transcriptomics identified 315 differentially expressed genes (DEGs) enriched in ciliary movement, neuroactive ligand-receptor interactions, and serotonergic synapses. Metabolomics identified 130 differentially abundant metabolites involved in arachidonic acid metabolism and serotonergic synapses. Integrated analysis highlighted correlative changes in the TM/5-HT signaling pathway. Phosphatidylinositol PI(16:0/20:2(11Z,14Z)) showed a strong positive correlation with Dbh gene expression, suggesting a candidate association between Dbh expression and phosphatidylinositol alterations. Gut microbiota analysis revealed compositional alterations (e.g., Muribaculaceae, Ileibacterium) and predicted functional shifts (e.g., tryptophan metabolism–related modules) were observed; these findings are exploratory. This study identifies multi-omics signatures associated with PFAS mixture-induced dopaminergic dysfunction in mice. The TM/5-HT pathway emerges as a candidate molecular axis requiring further investigation. Gut microbiota alterations suggest a potential peripheral component, but causality and gut-brain axis involvement remain hypothetical and need direct experimental validation. Full article

Vairimorpha ceranae (formerly Nosema ceranae) is an obligate intracellular parasite that poses a major threat to the health of the honey bee. Circular RNAs (circRNAs) have been recognized as key regulators in gene expression and pathogen–host interactions. However, their expression patterns and regulatory roles in V. ceranae infection remain largely unexplored. In this study, we performed circRNA profiling in V. ceranae spores (NcCK) and the midguts of Apis mellifera ligustica workers at 7 d post inoculation (dpi) and 10 dpi (Nc7T and Nc10T) based on transcriptome sequencing, followed by in-depth investigation of the regulatory roles of differentially expressed circRNAs (DEcircRNAs). In total, 243 circRNAs were identified in V. ceranae, with lengths predominantly ranging from 201 to 400 nucleotides. Comparative analysis screened 70 and 192 DEcircRNAs in the NcCK vs. Nc7T and NcCK vs. Nc10T comparison groups, respectively, with a significant majority being downregulated. The parental genes of these DEcircRNAs were significantly enriched in fundamental cellular processes and critical pathways such as protein processing in the endoplasmic reticulum and ribosome biogenesis. Additionally, we constructed a competing endogenous RNA network, suggesting that DEcircRNAs could potentially interact with DEmiRNAs to modulate mRNAs associated with fungal proliferation-relevant signaling pathways like MAPK, PI3K–Akt, and cAMP. Moreover, numerous DEcircRNAs were predicted to contain internal ribosome entry site elements, indicative of their potential for protein coding. The back-splicing junctions and expression trends of selected DEcircRNAs were successfully validated by RT-PCR and qRT-PCR. Our data not only offer a valuable resource for future functional studies but also provide a basis for elucidating the circRNA-mediated mechanisms underlying microsporidian pathogenesis and host–pathogen interactions. Full article

The scientific evidence regarding the use of plant-derived extracts to alleviate exercise-induced muscle damage in horses remains limited. Mulberry leaf flavonoids (MLFs) are the primary bioactive constituents of a traditional medicinal plant and are potent antioxidants. The aim of this study was to investigate the protective effects of MLFs against exercise-induced muscle damage. In this study, twelve Mongolian horses were used in a 3 × 3 Latin square design to investigate the protective effects of MLFs. Our results showed that high-intensity exercise negatively impacted the immune status, metabolic state, myofibrillar structure, and antioxidant capacity of the horses. Conversely, MLFs significantly reduced blood levels of white blood cells (WBC), monocytes (MON), aspartate aminotransferase (AST), creatine kinase (CK), and malondialdehyde (MDA) across various exercise distances and during recovery. Simultaneously, MLFs increased serum glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC). Mechanistically, transcriptomic analysis revealed that dietary MLFs upregulated genes associated with myofibrillar structural proteins (MYOZ2, MYOM3), the antioxidant defense system (GPX3, SOD3), and skeletal muscle satellite cell proliferation and differentiation (MYOD1, MRF6). Furthermore, quantitative proteomics indicated the enrichment of the PI3K-Akt and TGF-β signaling pathways, as well as ECM–receptor interactions, suggesting their potential involvement in regulating protein metabolism and facilitating myofibrillar restoration. Overall, MLFs effectively alleviated inflammation, metabolic disorder, and exercise-induced muscle damage. Under the tested conditions, a daily dosage of 10 g MLFs provided superior protective effects. Full article

Cutaneous squamous cell carcinoma (cSCC) is a common malignant skin tumor with invasive potential and risk of recurrence. This study investigated the anti-cSCC effects of luteolin in vitro and in vivo and explored the associated molecular mechanisms. The effects of luteolin on A431 cell viability were assessed by CCK-8 assay, and apoptosis was analyzed by Annexin V-FITC/propidium iodide (PI) double staining. qRT-PCR and Western blot analyses were performed to evaluate apoptosis-related factors and the EGFR/PI3K/AKT signaling pathway. Molecular docking was further conducted to explore the potential interactions of luteolin with EGFR/PI3K/AKT signaling-related proteins and apoptosis-associated proteins. In vivo, a two-stage skin carcinogenesis model induced by 7,12-dimethylbenz[a]anthracene (DMBA) and croton oil was used to evaluate the antitumor activity of luteolin. Luteolin significantly inhibited A431 cell viability and promoted apoptosis in a concentration-dependent manner. Moreover, luteolin increased Bax expression and decreased Bcl-2 expression at both the mRNA and protein levels. Mechanistically, luteolin suppressed the phosphorylation of EGFR, PI3K, and AKT. Molecular docking suggested that luteolin could interact with EGFR, PIK3CA, AKT, Bax, and Bcl-2, providing supportive in silico evidence for its potential modulation of EGFR/PI3K/AKT signaling and apoptosis-related proteins. In vivo, luteolin alleviated body weight loss, achieved a tumor nodule inhibition rate of 45.28%, significantly improved spleen and thymus indices (p < 0.05), and ameliorated histopathological damage in skin tissues. In addition, immunohistochemical analysis showed that luteolin reduced Ki-67 expression. These results indicate that luteolin exerts anti-cSCC effects in vitro and in vivo, possibly through modulation of the EGFR/PI3K/AKT signaling pathway and apoptosis-related proteins. Full article

Falls in older adults and individuals with balance impairments remain a major concern because they are closely associated with injury, reduced mobility, and loss of independence. This study presents a preclinical proof-of-concept for a cognitive smart walker architecture that combines user-compatible walking assistance with active safety intervention. The system integrates a 2D LiDAR sensor for contactless lower-limb monitoring, a six-degree-of-freedom (6-DOF) force/torque sensor to measure user–walker interaction, and an inertial measurement unit (IMU) for dynamic monitoring, with all data processed in real time on a Raspberry Pi/ROS-based platform. Normal walking assistance is provided through a command-level variable admittance-based controller that converts interaction forces into a smoothed signed duty-cycle command rather than a rigid speed-control signal. Safety decisions are managed by a Hierarchical State Machine (HSM). Early-risk conditions are handled through motor-based dynamic braking, whereas severe physical crises additionally deploy lateral support legs to enlarge the base of support. Within this framework, the system can detect and manage foot entanglement, grip loss, forward fall, vertical collapse, lateral fall, successive crises, and recovery-abort events. In experiments across multiple scenarios, the system correctly detected all 50 crisis cases and did not issue unnecessary interventions in 30 non-crisis cases. These findings show that the proposed architecture can preserve transparent walking assistance during normal gait while providing graded, context-sensitive active safety when risk emerges. Full article

The escalating demand for high-performance dielectric energy storage materials in pulse-power systems and portable electronics calls for polymer film capacitors with high discharged energy density and breakdown strength. Conventional polymers, however, suffer severe performance degradation under concurrent thermal and electrical stress, and existing reinforcement strategies—involving inorganic nanofillers or chemical crosslinking—often compromise flexibility, introduce interfacial defects, or involve complex processing. Herein, we demonstrate that incorporating a rigid mechanically interlocked molecule, specifically an octacationic homo[2]catenane, into a polyimide matrix yields robust, crosslink-like networks through strong [π∙∙∙π] electrostatic interaction between electron-rich aromatic units of polyimide and electron-deficient homo[2]catenane. This supramolecular network simultaneously enhances breakdown strength via densified chain packing and suppresses conduction loss by forming deep electron traps derived from the high electron affinity of homo[2]catenane. The optimized PI–HC⁸⁺ composite achieves a high discharged energy density of 7.86 J/cm³ with an efficiency > 80% and sustains stable performance over 10⁵ charge–discharge cycles at 150 °C. This research establishes mechanically interlocked molecules as a new class of functional fillers for high-performance polymer dielectrics, opening an unexplored avenue in the design of next-generation capacitive energy-storage materials. Full article

Colorectal cancer (CRC) is a multifactorial disease arising from dynamic interactions between gut microbiota, inflammatory processes, metabolic reprogramming, and dysregulated host signaling pathways. Increasing evidence highlights the potential of synbiotics—combinations of probiotics and prebiotics—as promising modulators of these processes. This review explores the mechanisms by which synbiotics influence CRC development and progression, integrating data from preclinical and clinical studies. Synbiotics exert beneficial effects by restoring microbial balance, enhancing the production of short-chain fatty acids (SCFAs), strengthening intestinal barrier integrity, and reducing chronic inflammation and oxidative stress. These functional changes converge on key molecular pathways, including Wnt/β-catenin, NF-κB, and PI3K/Akt/mTOR, which regulate tumor cell proliferation, survival, and immune responses. Preclinical studies consistently demonstrate anti-tumor effects, including reduced tumor growth, increased apoptosis, and modulation of the tumor microenvironment. Clinical evidence suggests that synbiotics may improve postoperative outcomes, reduce chemotherapy-related toxicity, and positively influence microbiome composition, although results remain heterogeneous. Emerging approaches focusing on microbiome profiling and personalized synbiotic interventions offer new opportunities for precision medicine in CRC. Overall, synbiotics represent a promising adjunctive strategy in colorectal cancer management, with potential to enhance therapeutic efficacy and improve patient outcomes. Further large-scale clinical studies are needed to validate their long-term benefits and establish standardized treatment protocols. Full article

Objectives: An infectious trigger can initiate a systemic inflammatory response, which in turn activates immune cells and causes the release of various mediators. Local mediators, such as resolvin D1 (RvD1), actively interact with immune cells to promote the resolution of inflammation. This study aimed to determine the impact of RvD1 on the inflammatory response mediated by monocytes in response to LPS. Methods: To investigate the mechanism by which RvD1 affects the monocyte-mediated inflammatory response to LPS, human THP-1 monocytic cells were treated with LPS, RvD1, or vehicle for 24 h. Inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α), were measured using enzyme-linked immunosorbent assay (ELISA). RNA sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs). The NF-κB and MAPK p38 signaling pathways were validated using real-time quantitative PCR (RT-qPCR) and Western blotting (WB). Results: RvD1 diminished the levels of IL-1β and TNF-α in LPS-induced inflammation. RvD1 significantly enhanced the mRNA expression of CREB, NRF2, and BCL-2. In addition, RvD1 significantly decreased the mRNA expression of CASP3. RvD1 regulated the inflammatory process in human monocytic THP-1 cells via the NF-κB p65 (MyD88, p65) and p38 MAPK signaling pathways (p38, BCL-2) and further suppressed the expression of apoptotic factors (PI3K, caspase-3). Conclusions: RvD1 has been shown to exert pro-resolving effects by regulating the anti-apoptotic gene BCL-2 and activating the NF-κB p65 and MAPK p38 signaling pathways. Full article

Background/Objectives: Over the past two decades, non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression, reshaping the classical view of the genome as predominantly protein-coding. Among them, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play central roles in controlling gene expression at multiple levels. Rather than acting independently, these molecules form complex and interconnected regulatory networks, and their interplay appears particularly relevant in cancer. This review aims to examine the mechanisms underlying miRNA-lncRNA cross-regulation and to explore their functional and clinical implications in tumor biology. Methods: We performed a comprehensive analysis of the current literature focusing on studies investigating miRNA-lncRNA interactions in cancer. Particular attention was given to mechanistic insights, including the competing endogenous RNA (ceRNA) hypothesis, as well as alternative regulatory models involving direct RNA interactions and chromatin-associated processes. Results: miRNA-lncRNA interactions have been associated with cancer progression and therapeutic response across different tumor types, although their mechanisms are highly context-dependent. While the ceRNA hypothesis, based on competition for shared microRNA response elements (MREs), provides a useful framework, it does not fully explain all observed phenomena. Evidence shows that miRNAs can directly regulate lncRNA stability, whereas lncRNAs can influence miRNA biogenesis. Additionally, chromatin-related mechanisms suggest that these interactions extend beyond post-transcriptional regulation. These RNA networks intersect with major oncogenic pathways, including PI3K/AKT/mTOR signaling, hypoxia responses, and epigenetic regulators such as EZH2, thereby affecting key cancer processes such as proliferation, epithelial–mesenchymal transition (EMT), and metabolic reprogramming. From a clinical perspective, the stability of ncRNAs in biological fluids highlights their potential as biomarkers. Combined miRNA-lncRNA signatures may improve diagnostic and prognostic accuracy compared to single markers, although further validation is required. Therapeutic strategies targeting ncRNA networks, such as miRNA mimics, antagomiRs, and lncRNA-directed approaches, are under investigation; however, challenges related to delivery, specificity, and toxicity remain. Conclusions: miRNA-lncRNA cross-regulation represents a complex and multifaceted layer of gene regulation in cancer. A deeper understanding of these interactions could support the development of more accurate diagnostic tools and more effective RNA-based therapeutic strategies, although significant technical and biological challenges still need to be addressed. Full article

Spatholobus suberectus is a medicinal and edible plant widely recognized for its pharmacological potential. Although its stems have been extensively studied and utilized, its leaves are often discarded as agricultural waste, leading to significant resource underutilization. To promote the sustainable valorization of these leaves, this study aimed to provide a predictive evaluation of their bioactive constituents and pharmacological potential. Leaves of S. suberectus were collected at six growth stages (January, March, May, July, September and November). A total of 6750 metabolites were identified, primarily comprising amino acids and derivatives (26.74%), organic acids (15.33%), and bioactive secondary metabolites, including flavonoids and phenolic acids (27.98%). Metabolic profiling revealed clear seasonal patterns, allowing the classification of the six harvest months into three distinct stages: January and March (G1), May and September (G2), and July and November (G3). Among these, the G1 stage was notably enriched in defensive secondary metabolites, particularly flavonoids and phenolic acids. To predict the bioactivity of these metabolites and elucidate potential mechanisms of action, network pharmacology and molecular docking analyses were employed. Network pharmacology and molecular docking were employed to predict anti-inflammatory mechanisms. From the metabolome, 83 potential bioactive compounds were screened, interacting with 306 targets. Network analysis identified 60 core anti-inflammatory targets (e.g., TNF, AKT1, PTGS2, STAT3) that were significantly enriched in MAPK and PI3K-Akt pathways. Molecular docking revealed strong binding affinities, with pelargonidin showing the highest affinity for PTGS2 (−11.72 kcal/mol). Candidate metabolites peaked in January, and extracts from this period exhibited notable COX-2 inhibitory activity (IC50 = 16.41 μg/mL). This research provides essential chemical characterization and preliminary bioactivity evidence to support the valorization of S. suberectus leaves and identifies January as the optimal harvest time to maximize their bioactive potential. Full article

Belonging to the Euphorbiaceae family, the Jatropha genus is a promising source for the discovery of antitumor compounds. Jatropha ribifolia is a traditionally used species in folk medicine in the semi-arid region of Brazil, with a few chemical and pharmacological reports. Based on that, the aim of the current work is to isolate, structurally characterize, and assess the cytotoxic activity of isolated compounds through in vitro and in silico analyses. To achieve these main goals, the underground parts were dried, extracted and purified using classical and instrumental chromatographic techniques, leading to the isolation of 16 compounds. Altogether with HR-ESI-MS, IR, one- and two-dimensional NMR experiments, eight previously unreported diterpenes, named ribifolones A-H, along with eight known compounds, were obtained and are herein described. Regarding their activity against melanoma (SK-MEL-28) and colorectal cancer (HCT-116) cell lines, jatrophone was the most potent with IC₅₀ values of 6.19 µM and 10.09 µM, followed by ribifolone C that exhibited a moderate cytotoxicity with IC₅₀ values of 50.71 µM and 33.39 µM, respectively. Network pharmacology analysis suggests the involvement of the PI3K-AKT-mTOR pathway in the activity of both compounds; meanwhile, molecular docking and dynamics simulations demonstrate the main interactions with key proteins in the pathway, indicating putative targets. This work opens new perspectives for the discovery of bioactive compounds found in Euphorbiaceae species, especially from those occurring in Caatinga. Full article

To address the key problems of low-frequency oscillation and insufficient regulation accuracy at the Point of Common Coupling (PCC) in hydro–wind–photovoltaic hybrid systems, which are caused by the randomness of wind and photovoltaic output, the water-hammer effect of hydropower units, and multi-source power coupling, a joint control strategy based on Fractional-Order Proportional Integral Derivative (FOPID) and Co-evolutionary Multi-objective Particle Swarm Optimization (CMOPSO) is proposed. First, a small-signal transfer function model of the system covering photovoltaic inverters, doubly fed induction generators (DFIGs), hydropower units and voltage-source converter-based high-voltage direct current (VSC-HVDC) converter stations is established to accurately characterize the water-hammer effect and multi-source dynamic coupling characteristics. Second, a Caputo-type FOPID controller is designed. Compared with traditional integer-order controllers with limited tuning flexibility, the FOPID controller utilizes its five degrees of freedom to address specific multi-source coupling challenges. This precisely compensates for the non-minimum phase lag caused by the water-hammer effect in hydropower units via the fractional derivative link, and effectively smooths the impact of stochastic wind–solar fluctuations on PCC voltage through the memory characteristics of the fractional integral link. This multi-parameter regulation mechanism prevents a trade-off between response speed and overshoot suppression, achieving effective decoupling of complex multi-source dynamic interactions. Third, a dual-objective optimization framework with the Integral of Time-weighted Absolute Error (ITAE) and Oscillatory Disturbance Risk Index (ODRI) as the objectives is constructed. The multi-population co-evolution mechanism of the CMOPSO algorithm is adopted to solve the Pareto-optimal solution set, realizing the coordinated optimization of dynamic response accuracy and oscillation instability risk. Finally, comparative simulations are carried out on the Simulink platform with traditional PI/FOPI controllers and optimization algorithms such as Multi-objective Particle Swarm Optimization based on the Decomposition/Simple Indicator-Based Evolutionary Algorithm (MPSOD/SIBEA). The results show that the proposed strategy can effectively suppress low-frequency oscillations in the range of 0~30 Hz. Compared with the traditional PI controller, the PCC voltage overshoot is reduced by more than 40%, the oscillation decay time is shortened by 33%, the ITAE and ODRI indices are decreased by 12.58% and 2.47%, respectively, and the stability of DC bus voltage is significantly improved. Its robustness and comprehensive control performance are superior to existing methods, providing an efficient and stable control scheme for power electronics-dominated complex new energy grid-connected systems. Full article

Phosphate (Pi) and calcium (Ca²⁺) are essential mineral ions that play coordinated roles in maintaining normal cellular functions. While various steps of calcium signaling are well characterized, emerging evidence suggests the critical role of both intracellular and extra cellular phosphate in regulating intracellular Ca²⁺. In the cytoplasm, phosphate influences ATP production and organelle calcium buffering and influences the activity of calcium pumps, such as sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase (SERCA) and the plasma membrane Ca²⁺-ATPase (PMCA). Extracellular phosphate, taken up via sodium-dependent phosphate transporters, triggers signaling cascades that affect the processes of calcium influx, storage, and release. Additionally, high extracellular phosphate levels can disrupt calcium homeostasis through the systemic interactions of hormones such as fibroblast growth factor 23 (FGF23), vitamin D and parathyroid hormone (PTH), especially under pathological conditions such as chronic kidney disease (CKD). This article briefly summarizes the current understanding of the bidirectional influence of intra- and extracellular phosphate on calcium dynamics at the cellular level, with a focus on the underlying mechanisms. Full article