Search Results (4,556)

To optimize the oxygen reduction reaction activity and long-term stability of the PrBaFe₂O_6-δ (PBF) cathode for protonic ceramic fuel cell (PCFC), this study employed the sol–gel method to dope Sc at the Fe-site of PBF, preparing a novel PrBaFe_1.8Sc_0.2O_6-δ (PBFS) cathode. The effects of different sintering temperatures on the phase composition, microstructure, and electrochemical performance of the PBFS cathode were systematically studied. Results showed that the PBFS cathode sintered at 1000 °C formed a single cubic perovskite structure, exhibiting excellent chemical compatibility with the electrolyte. Sc doping induced Fe in the cathode to exhibit a mixed valence state of Fe²⁺/Fe³⁺/Fe⁴⁺, thus significantly increasing the oxygen vacancy concentration. The single cell assembled achieved a peak power density of 1.303 W·cm⁻² and a polarization resistance as low as 0.035 Ω·cm² with H₂ as the fuel at 700 °C. Moreover, after 100 h of long-term operation at 650 °C, the power density decayed by only 5.23%, thus demonstrating excellent long-term stability. This study offers an efficient cobalt-free cathode candidate for PCFC. Full article

Marine-derived natural products are increasingly recognized for their therapeutic potential in cancer and other chronic diseases. Despite significant advances, current cancer treatments remain challenged by toxicity, drug resistance, and limited survival benefits. Natural compounds offer promising alternatives due to their multi-target mechanisms and favorable safety profiles. Among them, Spirulina, a filamentous cyanobacterium, stands out for its rich composition and diverse biological activities. Its anticancer effects involve apoptosis induction via intrinsic and extrinsic pathways, cell cycle arrest at G1/S or G2/M phases, inhibition of angiogenesis through the VEGF/VEGFR2 axis, and suppression of epithelial–mesenchymal transition. These activities are mainly attributed to C-phycocyanin, allophycocyanin, phenolic compounds, and immunomodulatory polysaccharides. Spirulina also exhibits potent immunomodulatory effects by enhancing natural killer cell activity, promoting M1 macrophage polarization, and regulating Th1 and Th17 cytokine responses, highlighting its potential as both an immunotherapeutic and chemoprotective agent. Moreover, preclinical findings suggest it may reduce chemotherapy-associated side effects. However, translation into clinical therapy remains limited by low bioavailability, lack of standardized extracts, and scarce clinical evidence. This review summarizes current mechanistic and immunological insights and highlights the need for optimized formulations, defined dosing strategies, and well-designed clinical trials to validate Spirulina’s potential in cancer treatment. Full article

The development of planar structures such as wings or leaves is a common feature among organisms and serves as a mechanism to increase surface to volume ratios. We wished to explore whether the recurrent and independent development of similar adaptive planar morphologies is the result of an activation of common genetic modules or toolkits. To test this, we focused on the developmental gene networks that are proposed to define leaf polarity in eudicots in phylloclades, leaf-like organs derived from branch primordia, in the monocot Ruscus aculeatus. Since branch primordia normally have a radial shape, this approach allowed us to examine the genetic changes required for the transformation from a round to a planar (flat) form. In our transcriptome analysis of phylloclade and stem tissue, we detected 76,085 annotated ORFs of which 87.2% were identified as complete out of 2026 BUSCO groups. Expression patterns clearly identify differentiation between phylloclade and stem tissues consistent with an enhanced photosynthetic function in the phylloclades. However, except for the AS1/AS2 and possibly STM module, we see little evidence that canonical leaf adaxial and abaxial modules are activated in the sampled phylloclades compared with the stems. Our results show that the unifacial nature of phylloclades is consistent with the observed lack of strong adaxial/abaxial molecular signatures. We propose that in R. aculeatus and plants with similar unifacial laminar leaves, adaxial/abaxial molecular identity may not be required for planar growth, and that lateral expansion of organ primordia and acropetal and intercalary cell division may be sufficient to generate planar versus radial organ shapes. Full article

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) represents a dynamic and multistage pathological process driven by maladaptive intercellular communication. Rather than resulting from isolated cellular injury, AKI-CKD progression unfolds through a spatially and temporally coordinated dysregulation of cellular networks. In the acute phase, damaged tubular epithelial cells act as instigators, releasing damage-associated molecular patterns (DAMPs) and activating a storm of inflammatory crosstalk among immune cells, endothelium, and fibroblasts. During the subacute repair phase, imbalance in macrophage polarization (M1 persistence/M2 dysfunction) and the emergence of senescent tubular cells with a senescence-associated secretory phenotype (SASP) together create a pro-fibrotic microenvironment. In the chronic phase, activated myofibroblasts—derived from multiple sources—establish self-sustaining feedback loops via autocrine signaling, mechanical memory from the stiffened extracellular matrix (ECM), and ongoing dialogue with immune and resident cells, ultimately leading to irreversible fibrosis. Current therapeutic strategies focused on single molecular targets often fail to disrupt this resilient network homeostasis. Therefore, we propose a paradigm shift toward spatiotemporally precise network-remodeling therapies, which require integrated use of liquid biopsy-based staging, smart nanocarriers for cell-specific delivery, and AI-powered multi-omics modeling. This review systematically delineates the evolving cell-to-cell communication networks across AKI-CKD continuum and highlights innovative strategies to intercept disease progression by targeting the pathophysiology of cellular crosstalk. Full article

Temporomandibular disorders (TMDs) are multifactorial conditions traditionally attributed to excessive mechanical loading on the temporomandibular joint, leading to clinical manifestations ranging from joint sounds to structural deformation. Contributing factors include trauma, occlusal abnormalities, psychological stress, and bruxism. However, immune and molecular alterations associated with early disease activity are not systematically integrated into structure-centered TMD frameworks. Emerging evidence indicates that temporomandibular joint osteoarthritis (TMJOA) involves activation of innate immunity caused by damage-associated molecular patterns (DAMPs) generated through mechanical loading, together with non-antigen-specific adaptive immune responses, including macrophage polarization and T helper 17 (Th17) and regulatory T (Treg) cell imbalance. Inflammatory and mechanical inputs converge through shared signaling modules and mechanoresponsive transcriptional programs, promoting extracellular matrix degradation, fibrotic remodeling, and subchondral bone remodeling. This review synthesizes the current immunopathological and mechanobiological evidence and introduces temporomandibular immunologic disease (TMID) as a mechanism-oriented framework, characterized by a reinforcing cycle between mechanically induced tissue damage and immune activation within the temporomandibular joint (TMJ) microenvironment. TMID complements TMJOA and Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) structural diagnostic categories while excluding antigen-specific autoimmune arthritides such as rheumatoid arthritis, thus functioning as a mechanistic overlay framework for the integration of immuno-mechanical signaling networks in immune-active, mechanically driven TMJ pathology. Full article

Titanium implants are widely used in orthopedic and dental fields but often face challenges such as insufficient osseointegration and peri-implant inflammation. While Strontium (Sr) possesses potent bioactive properties, achieving its controlled delivery at the implant-tissue interface remains technically challenging. To address this, we engineered a multidimensional composite coating by constructing a micro/nano-porous TiO₂ substrate via micro-arc oxidation (MAO), followed by polydopamine (PDA)-assisted Sr immobilization. This integrated architecture significantly enhanced surface hydrophilicity and facilitated high-content Sr loading with sustained release kinetics. Biological evaluations demonstrated that the PDA-mediated interface promoted superior initial adhesion and spreading of bone marrow mesenchymal stem cells (BMSCs), synergizing with released Sr²⁺ to markedly upregulate core osteogenic markers (Runx2, ALP). Crucially, the functionalized surface actively optimized the immune microenvironment by inducing M1-to-M2 macrophage polarization and comprehensively suppressing RANKL-induced osteoclastogenesis via the downregulation of TRAP and DC-STAMP. By integrating these pro-osteogenic, anti-inflammatory, and anti-resorptive capabilities, this tri-functional system effectively rebalances the bone remodeling microenvironment. Consequently, it provides a robust, universally applicable strategy for enhancing the therapeutic efficacy of next-generation orthopedic and dental implants. Full article

Cutaneous T-cell lymphoma (CTCL) comprises a heterogeneous group of extranodal non-Hodgkin lymphomas. With the publication of the fifth edition of the World Health Organization Classification of Hematolymphoid Tumors, the diagnostic framework for CTCL has shifted from primarily morphologic phenotypes toward an emphasis on molecular drivers. Current research suggests that malignant clones may arise from somatic mutations at the hematopoietic stem cell stage and may follow a continuous hematogenous dissemination model with bidirectional trafficking between the skin and systemic circulation. At the molecular level, genomic instability, often associated with somatic copy-number variations, may promote activation of the janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway through gene-dosage effects. In parallel, chromatin remodeling linked to EZH2 overexpression and reduced special SATB1 expression may support a Th2-polarized program. This phenotype may contribute to epidermal barrier impairment via cytokines such as Interleukins-4 (IL-4) and IL-13, potentially creating conditions permissive for Staphylococcus aureus colonization. Microbial superantigens and exotoxins may further contribute to tumor progression and therapeutic resistance by reinforcing JAK/STAT signaling, particularly STAT3, and reducing CD8+ T-cell–mediated immune surveillance. In the dermis, reprogramming of cancer-associated fibroblasts and polarization of macrophages toward an M2 phenotype may collectively contribute to an immunosuppressive niche. Emerging biomarkers, including CD74, and acquired resistance mechanisms after anti-C-C chemokine receptor 4 therapy further extend the translational relevance of recent pathologic findings. Overall, CTCL evolution appears to be a systemic process shaped by interactions between tumor-intrinsic genetic alterations and the skin microenvironment. Full article

Cancer remains a leading cause of morbidity and mortality globally, with current therapies often limited by toxicity, drug resistance, and reduced efficacy in advanced stages. Medicinal plants represent important sources of bioactive compounds (BACs) with anticancer and chemopreventive potential; however, their successful application is strongly influenced by extraction strategies that determine phytochemical recovery and downstream biological activity. This review evaluates solvent-based extraction techniques used to extract BACs from medicinal plants with reported anticancer properties, synthesizing peer-reviewed articles from PubMed and Google Scholar published between 2020 and 2025. Solvent-based methods, including Soxhlet and maceration, were most widely applied due to their operational simplicity and the preservation of structurally diverse metabolites while percolation, decoction, infusion, and hydro-distillation were sparsely utilized. Extraction strategy and solvent polarity emerged as primary factors shaping phytochemical profiles, with phenolics, flavonoids, alkaloids, and terpenoids identified as dominant classes. Reported half maximal inhibitory concentration (IC₅₀) ranged from highly potent (0.12 µg/mL) to weak (30,000 µg/mL), reflecting variability driven by extraction parameters and plant matrix complexity. Anticancer mechanisms commonly involved apoptosis induction, cell-cycle arrest, reactive oxygen species-mediated cytotoxicity, and inhibition of proliferative signaling pathways across breast, cervical, colon, lung, liver, and prostate cancer models. Although solvent-based extraction approaches remain widely used, their context-dependent nature and lack of standardization limit reproducibility. Overall, anticancer and chemotherapeutic efficacy is primarily governed by BAC composition, while extraction methods act as upstream modulators. Future progress requires phytochemical-informed, standardized workflows supported by hybrid extraction systems, AI-assisted optimization, and advanced bioavailability and delivery systems to enable reproducible and clinically relevant translation of plant-derived chemotherapeutics. Full article

Pesticides are a major cause of water contamination, making this issue a major environmental and public health concern. In this context, the development of advanced and effective remediation materials is needed. In this study, a titanium-functionalized magnetic silica aerogel (AG-Ti@Fe₃O₄-SA) was successfully prepared via microfluidics and evaluated for water decontamination. The structural and compositional features of the aerogel were determined using XRD, FT-IR, RAMAN, SEM, TEM, BET, and DLS, confirming the formation of the aerogel with dispersed Fe₃O₄-SA nanoparticles and the successful incorporation of titanium within the aerogel matrix. Regarding decontamination potential, the aerogel was tested against a pesticide mixture, yielding pesticide-dependent removal efficiencies (16–100%). Notably, the aerogel exhibited a high affinity for organophosphorus pesticides and a moderate affinity for polar compounds, whereas bulky hydrophobic pesticides showed lower adsorption. In vitro, the aerogel induced a moderate decrease in HaCaT cell viability after 48 h of exposure, accompanied by a slight increase in lactate dehydrogenase release, while HEK293 cells remained largely unaffected, indicating a cell-type-dependent biological response. Overall, the findings from this screening-level study recommend AG-Ti@Fe₃O₄-SA aerogel as a promising selective adsorbent for pesticide removal. Full article

Helichrysum italicum Mill. (Asteraceae), a perennial evergreen species native to the Mediterranean basin, has been traditionally employed to treat various inflammatory and infectious diseases, as well as respiratory, digestive, gallbladder, and bladder disorders. The plant is valued for its essential oil. It contains phenols and flavonoids, which play a fundamental role in the protective effects associated with the traditional use of extracts of its aerial parts. The goal of the study was to investigate the phytochemical and biological properties of polar extracts, specifically water and hydroalcoholic (50% ethanol) extracts, obtained from the aerial parts of H. italicum. The extracts were evaluated for phenolic composition and concurrently assessed for antioxidant and enzyme-inhibitory activities. Additionally, the biocompatibility of the extracts was investigated using eco-toxicological models, including Artemia salina lethality and Daphnia magna cardiotoxicity assays, as well as allelopathic studies. CCD841CoN colon epithelial cell viability was also assessed in the presence of the extracts. The extracts’ protective effects were examined in an ex vivo inflammatory model using isolated mouse colon and liver tissues exposed to Escherichia coli lipopolysaccharide (LPS). Their influence on cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) gene expression was investigated, as well. Docking studies were also performed to uncover on the potential mechanisms underpinning the biological effects observed in the study. The phytochemical analysis showed that hydroxycinnamic acids and quercetin derivatives were the primary components in both extracts. In particular, the hydroalcoholic extract showed higher phenol levels and more potent scavenging/reducing and enzyme inhibitory activities against tyrosinase, cholinesterases, glucosidase, and amylase. Using the aforementioned eco-toxicological and in vitro cell models, the extracts’ biocompatibility was determined to be in the range of 200–1000 µg/mL. Within this concentration interval, the extracts effectively mitigated LPS-induced stimulation of COX-2 and IL-6 gene expression. Docking studies suggest that hydroxycinnamic acids (notably chlorogenic acid) and flavonoids (including quercetin, rutin, hyperoside, and isoquercitrin) play a pivotal role in the extracts’ anti-inflammatory activity. In conclusion, this study provides scientific evidence supporting the ethnopharmacological use of H. italicum in managing oxidative stress and inflammatory disorders, especially in the digestive system. Phenolics in the extracts likely enhance their therapeutic potential. These findings warrant further research, including in vivo studies, to assess the extracts’ efficacy and safety profile comprehensively. Full article

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis larvae, is a severe zoonotic disease mimicking tumors, primarily affecting the liver with high mortality if untreated. Host immunity plays a pivotal role, shifting from Th1/Th17-mediated clearance to Th2/Treg-driven tolerance, enabling parasite survival. Liver macrophages, including Kupffer cells, polarize towards M2 phenotype under parasite antigens (e.g., phytic acid, exosomes), promoting immunosuppression, fibrosis, and T cell exhaustion via IL-10/TGF-β. This reshapes the tumor-like immune microenvironment with M2 macrophages recruiting Tregs, suppressing NK/DC functions, and fostering angiogenesis/fibrosis. Current treatment remains centered on surgery and benzimidazole therapy, both of which have notable limitations. Experimental immunomodulatory strategies, drug repurposing approaches, and targeted delivery systems may offer future therapeutic opportunities, but these concepts remain largely preclinical, unproven in AE, and require careful evaluation for safety and efficacy. Full article

This commentary critically evaluates the translational relevance of a recent study investigating the effects of ozonated saline solution (O₃SS) on microglial and endothelial cell models. While the original research proposes potential antioxidant and anti-inflammatory benefits of low-dose ozone exposure, we identify significant methodological and conceptual flaws that undermine its conclusions. Key concerns include the unjustified assumption that ozone behaves similarly in microwell cultures and clinical infusion settings, despite known physicochemical differences affecting ozone stability and reactivity. The use of immortalized BV2 and HUVEC cells, which lack the complexity of in vivo systems, further limits the study’s applicability. The absence of accurate ozone quantification, proper controls, protein-level validation, and kinetic modeling exacerbates these weaknesses. Our analysis also demonstrates, through differential equation modeling, that ozone rapidly decays in saline solutions, making systemic delivery via infusion chemically implausible as a therapeutic approach. Moreover, the extrapolation of in vitro gene expression data to systemic therapeutic claims lacks scientific justification. We conclude that while the observed cellular responses in vitro are of academic interest, they do not support the efficacy or safety of O₃SS in clinical settings. A more rigorous approach is necessary to substantiate the biomedical potential of ozonated solutions. Full article

Background and Objectives: Mycosis fungoides (MF) is the predominant subtype of cutaneous T-cell lymphoma, whereas large plaque parapsoriasis (LPP) closely resembles early-stage MF, making differential diagnosis challenging. Immune markers, such as CD47, CD163, and B7-H3, play crucial roles in tumor immune evasion and macrophage polarization. However, their expression profiles and potential diagnostic or prognostic implications in early-stage MF and LPP remain poorly defined. Therefore, this study aimed to evaluate the expression of CD47, CD163, and B7-H3 in early-stage MF and LPP and analyze their associations with clinicopathological characteristics and patient outcomes. Materials and Methods: This retrospective study evaluated the immunohistochemical expression of CD47, CD163, and B7-H3 in 46 patients with early-stage mycosis fungoides (MF) and 46 patients with large plaque parapsoriasis (LPP). Expression levels were assessed using an immunoreactivity scoring system and analyzed for their associations with clinical parameters and disease-free survival (DFS). The study included patients diagnosed and followed at Sivas Cumhuriyet University between 1 March 2015 and 31 March 2025. Results: High CD47 expression was detected in 72.7% of MF patients, high B7-H3 expression in 45.7%, and high CD163 expression in 46.7% compared with LPP patients (p < 0.001). These markers showed positive correlations, and elevated expression, especially of B7-H3 and CD163, was associated with shorter disease-free survival in univariate analysis. Conclusions: The higher expression of CD47, CD163, and B7-H3 in early-stage MF compared with LPP suggests that these markers may contribute to the differential diagnosis and could represent potential therapeutic targets; however, their independent prognostic value requires confirmation in larger studies. Full article

The immune system is a pivotal regulator of reproductive physiology, maintaining tissue homeostasis essential for successful pregnancy while contributing to infertility and reproductive disorders when dysregulated. Natural products represent a valuable source of novel immunomodulatory agents. Icariin (ICA), a prenylated flavonoid glycoside isolated from Epimedium species (Horny Goat Weed), has a long-standing traditional use for “invigorating yang,” which modern research attributes to its reproductive function-enhancing properties. This review synthesizes emerging evidence that the beneficial effects of ICA on female and male reproductive health are primarily mediated through its sophisticated immunomodulatory actions on the reproductive–immune axis. We systematically dissect the molecular mechanisms by which ICA reprograms the reproductive immune microenvironment, focusing on its regulation of macrophage polarization, T-helper cell (Th1/Th2/Th17) and regulatory T-cell (Treg) balance, and suppression of key pro-inflammatory signaling pathways (NF-κB, NLRP3 inflammasome, JAK-STAT) in ovarian, uterine, and testicular tissues. This review provides a detailed account of how ICA modulates reproductive disorders via regulating immune responses, with the aim of offering innovative strategies for the design of novel immunomodulatory therapies targeting reproductive diseases. Full article

This study proposes a novel state of health (SOH) estimation method by extracting two-level hierarchical features linked to fundamental degradation mechanisms. At the module level, the length of the incremental power curve during constant current charging is extracted, capturing cumulative effects of subtle changes. At the cell level, a combined temperature-weighted voltage inconsistency curve is constructed. The state of charge (SOC) at its distinct knee point within the high-SOC range is a key indicator, signifying the accelerated failure stage where polarization and thermoelectric feedback intensify. This knee-point SOC quantitatively reflects the degree of SOH degradation, making it a valid feature for accurate SOH estimation. The proposed Temporal Convolutional Network–Transformer–Squeeze-and-Excitation (TCN–Transformer–SE) model assigns weights to these features via Squeeze-and-Excitation (SE) and uses Temporal Convolutional Network (TCN) and Transformer branches for parallel local and global temporal decisions. Aging experiments demonstrate the method’s superiority through multi-feature comparison, ablation studies, and benchmark evaluation, achieving a maximum mean absolute error (MAE) of 0.0031, a root mean square error (RMSE) of 0.0038, a coefficient of determination (R²) of 0.9937 and a mean absolute percentage error (MAPE) of 0.3820. The work provides a fusion estimation framework with enhanced interpretability grounded in electrochemical analysis. Full article