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26 pages, 2374 KB  
Article
Native Plant Responses and Elemental Accumulation in Mining and Metallurgical Mediterranean Ecosystems
by Eleni G. Papazoglou, Hamza Zine, Panayiotis Trigas, Małgorzata Wójcik and Jaco Vangronsveld
Plants 2025, 14(17), 2646; https://doi.org/10.3390/plants14172646 (registering DOI) - 25 Aug 2025
Abstract
Mining and metallurgical activities negatively impact ecosystems due to the release of potentially toxic elements (PTEs). This study assesses PTE pollution and accumulation in native plant species that have spontaneously colonized a historical mining site (Michaly, site A) and a nearby metallurgical smelter [...] Read more.
Mining and metallurgical activities negatively impact ecosystems due to the release of potentially toxic elements (PTEs). This study assesses PTE pollution and accumulation in native plant species that have spontaneously colonized a historical mining site (Michaly, site A) and a nearby metallurgical smelter site (Varvara, site B) on the Lavreotiki Peninsula, Attika, Greece. Soils were analyzed for As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sb, and Zn. A total of 89 native plant taxa across 28 families were identified. The aerial parts from dominant species were analyzed for PTE concentrations, and bioconcentration factors (BCFs) were calculated. One-way ANOVA and principal component analysis (PCA) using R were used for statistical evaluation. Soils at both sites showed elevated As, Cd, Cr, Cu, Ni, Pb, Sb, and Zn; Mn was high only at site B, while Co and Fe remained at background levels. Several plant species, especially at Michaly, had elevated concentrations of As, Cd, Co, Cr, Fe, Pb, Sb, and Zn in their aerial parts. BCFs indicated general PTE exclusion from aerial parts, particularly at site B. Native vegetation on these contaminated sites shows resilience and PTE exclusion, highlighting their potential for phytoremediation, especially phytostabilization, and ecological restoration in similarly polluted Mediterranean environments. Full article
16 pages, 3443 KB  
Article
Immunohistochemical Characterisation of the Interstitial Inflammatory Environment: T-Cell- and B-Cell-Dominant Subtypes of Hidradenitis Suppurativa
by Nessr Abu Rached, Stefanie Bruckmüller, Martin Doerler, Hanna Telkemeyer, Lennart Ocker, Yannik Haven, Daniel Myszkowski, Markus Stücker, Eggert Stockfleth and Falk G. Bechara
Dermatopathology 2025, 12(3), 25; https://doi.org/10.3390/dermatopathology12030025 (registering DOI) - 25 Aug 2025
Abstract
Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a complex immune response. Given the considerable heterogeneity of the clinical phenotype of HS, this study aimed to analyse the immunohistochemical pattern of interstitial inflammation. Methods: Immunohistochemical analysis was performed on skin samples [...] Read more.
Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a complex immune response. Given the considerable heterogeneity of the clinical phenotype of HS, this study aimed to analyse the immunohistochemical pattern of interstitial inflammation. Methods: Immunohistochemical analysis was performed on skin samples from 49 patients with HS. The immunohistochemical markers CD3, CD4 and CD8 for T-cells, CD20 for B-cells, CD138 for plasma cells and CD30, CD56, Bcl-2 and Bcl-6 were stained on lesional skin. Results: The analysis of immune cell dominance in patients with HS revealed that 33.3% of the cohort exhibited B-cell dominance, defined as a ratio of the sum of CD20+ and CD138+ cells to CD3+ cells greater than 1, while the majority (66.7%) demonstrated T-cell dominance, defined as a ratio of CD3+ cells to the sum of CD20+ and CD138+ cells greater than 1. B-cell-dominant HS is associated with a significantly elevated probability of mammary involvement (13.3% vs. 0%; p = 0.041). T-cell-dominant HS patients tended to demonstrate a higher mean tobacco consumption, but not significantly (20 vs. 5 tobacco pack-years; p = 0.06). CD4-dominant HS patients exhibited a significantly greater involvement of the mons pubis (62.5% vs. 28.6%, p = 0.023) compared to CD8-dominant patients, who demonstrated a significantly higher number of abscesses (p = 0.027). Conclusions: For the first time, we describe the clinical and immunohistochemical characteristics of T-cell- and B-cell-dominant HS. Although HS seems to be more dominated by T-cells, a B-cell dominance was found in 33% of cases. Full article
(This article belongs to the Section Clinico-Pathological Correlation in Dermatopathology)
21 pages, 4783 KB  
Article
Epithelial-Mesenchymal Transition Activates YAP to Drive Malignant Progression and Immune Evasion
by Xi Huang, Mingyan Zhang, Alexander D. Pearce, Matthew D. Gibbons, Dan Jin, Lu Li, Dongxin Hu, Renbin Liu, Mu Yu, Ming Tan, Jia Chang, Jixin Dong, Mingyi Xie, Weizhou Zhang, Lizi Wu, Catherine Flores, Jörg Bungert, Todd M. Brusko and Jianrong Lu
Cancers 2025, 17(17), 2767; https://doi.org/10.3390/cancers17172767 (registering DOI) - 25 Aug 2025
Abstract
Background: Epithelial-mesenchymal transition (EMT) is prevalent in human cancer and facilitates tumor metastasis and therapy resistance by enhancing cancer cell motility, invasiveness, survival, and immune evasion. However, the molecular mechanisms underlying the cellular changes during EMT remain largely elusive, making it challenging [...] Read more.
Background: Epithelial-mesenchymal transition (EMT) is prevalent in human cancer and facilitates tumor metastasis and therapy resistance by enhancing cancer cell motility, invasiveness, survival, and immune evasion. However, the molecular mechanisms underlying the cellular changes during EMT remain largely elusive, making it challenging to simultaneously target these diverse malignant phenotypes. Results: Here, we show that the EMT-inducing ZEB transcription factors directly repressed WWC1 (also known as KIBRA), a key upstream activating component of the Hippo signaling pathway. The EMT program thus inherently downregulated WWC1, leading to impaired Hippo signaling and constitutive activation of the downstream effector and transcriptional coactivator YAP. The YAP-dependent transcriptional program promotes manifold cellular phenotypes that resemble those induced during EMT. Indeed, pharmacological inhibition of YAP suppressed EMT-stimulated cell migration and invasion, apoptosis resistance, and cell size growth, identifying active YAP as a common essential mediator of multiple EMT-associated phenotypes. Moreover, YAP activation directly induced transcription of B7 family immune checkpoint proteins VSIR (VISTA) and PD-L2, and rendered cancer cells resistant to effector CD8 T cells. Conclusions: Collectively, the results suggest that EMT intrinsically activates YAP by repressing WWC1, providing a non-genetic mechanism for pervasive YAP activation in cancer. Activated YAP, in turn, critically contributes to diverse EMT-enhanced malignant phenotypes and immune evasion. Therefore, pharmacological targeting of YAP may suppress various EMT-associated malignant properties and improve the efficacy of anti-PD-1 immunotherapy, offering a promising therapeutic strategy against cancer cells exhibiting EMT characteristics. Full article
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22 pages, 5532 KB  
Article
OFNet: Integrating Deep Optical Flow and Bi-Domain Attention for Enhanced Change Detection
by Liwen Zhang, Quan Zou, Guoqing Li, Wenyang Yu, Yong Yang and Heng Zhang
Remote Sens. 2025, 17(17), 2949; https://doi.org/10.3390/rs17172949 (registering DOI) - 25 Aug 2025
Abstract
Change detection technology holds significant importance in disciplines such as urban planning, land utilization tracking, and hazard evaluation, as it can efficiently and accurately reveal dynamic regional change processes, providing crucial support for scientific decision-making and refined management. Although deep learning methods based [...] Read more.
Change detection technology holds significant importance in disciplines such as urban planning, land utilization tracking, and hazard evaluation, as it can efficiently and accurately reveal dynamic regional change processes, providing crucial support for scientific decision-making and refined management. Although deep learning methods based on computer vision have achieved remarkable progress in change detection, they still face challenges including reducing dynamic background interference, capturing subtle changes, and effectively fusing multi-temporal data features. To address these issues, this paper proposes a novel change detection model called OFNet. Building upon existing Siamese network architectures, we introduce an optical flow branch module that supplements pixel-level dynamic information. By incorporating motion features to guide the network’s attention to potential change regions, we enhance the model’s ability to characterize and discriminate genuine changes in cross-temporal remote sensing images. Additionally, we innovatively propose a dual-domain attention mechanism that simultaneously models discriminative features in both spatial and frequency domains for change detection tasks. The spatial attention focuses on capturing edge and structural changes, while the frequency-domain attention strengthens responses to key frequency components. The synergistic fusion of these two attention mechanisms effectively improves the model’s sensitivity to detailed changes and enhances the overall robustness of detection. Experimental results demonstrate that OFNet achieves an IoU of 83.03 on the LEVIR-CD dataset and 82.86 on the WHU-CD dataset, outperforming current mainstream approaches and validating its superior detection performance and generalization capability. This presents a novel technical method for environmental observation and urban transformation analysis tasks. Full article
(This article belongs to the Special Issue Advances in Remote Sensing Image Target Detection and Recognition)
12 pages, 1894 KB  
Article
Pyrometallurgical Process to Recover Lead and Silver from Zinc Leaching Residue
by Cancio Jiménez-Lugos, Manuel Flores-Favela, Antonio Romero-Serrano, Aurelio Hernández-Ramírez, Alejandro Cruz-Ramírez, Enrique Sanchez-Vite, José Ortiz-Landeros and Eduardo Colin-García
Recycling 2025, 10(5), 167; https://doi.org/10.3390/recycling10050167 (registering DOI) - 25 Aug 2025
Abstract
During the roasting, leaching, and electrodeposition of zinc ores, lead–silver residues are produced. These residues contain valuable metals (Pb, Zn, and Ag) and toxic metals (Cd and As). In this study, a pyrometallurgical process is proposed for treating Pb-Ag residues, consisting of drying, [...] Read more.
During the roasting, leaching, and electrodeposition of zinc ores, lead–silver residues are produced. These residues contain valuable metals (Pb, Zn, and Ag) and toxic metals (Cd and As). In this study, a pyrometallurgical process is proposed for treating Pb-Ag residues, consisting of drying, roasting, and reduction steps to recover valuable metals, such as silver in a metallic Pb phase, while converting the waste into an environmentally friendly slag. First, the Pb-Ag residue is dried at 100 °C, then roasted at 700 °C, and finally reduced at a high temperature, with Na2CO3 as a flux and CaSi as a reducing agent, rather than carbon-based reducing agents (carbon or carbon monoxide), to minimize greenhouse gas production. The effects of the reduction temperature and the mass of the reducing agent were investigated on a laboratory scale. The metallic phase and slag obtained in the reduction step were characterized by their chemical composition and mineralogy via chemical analysis, X-ray diffraction, and SEM-EDS. The results showed that silver and lead formed a metallic phase, and that silver content decreased from 1700 ppm in the Pb-Ag residue to 32 ppm in the final slag at 1300 °C. The Pb-Ag residue and final slag were leached with an aqueous acetic acid solution to evaluate their chemical stability. Full article
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16 pages, 2459 KB  
Article
Technoeconomic Assessment of Biogas Production from Organic Waste via Anaerobic Digestion in Subtropical Central Queensland, Australia
by H. M. Mahmudul, M. G. Rasul, R. Narayanan, D. Akbar and M. M. Hasan
Energies 2025, 18(17), 4505; https://doi.org/10.3390/en18174505 (registering DOI) - 25 Aug 2025
Abstract
This study evaluates biogas production through the anaerobic digestion of food waste (FW), cow dung (CD), and green waste (GW), with the primary objective of determining the efficacy of co-digesting these organic wastes commonly generated by households and small farms in Central Queensland, [...] Read more.
This study evaluates biogas production through the anaerobic digestion of food waste (FW), cow dung (CD), and green waste (GW), with the primary objective of determining the efficacy of co-digesting these organic wastes commonly generated by households and small farms in Central Queensland, Australia. The investigation focuses on both experimental and technoeconomic aspects to support the development of accessible and sustainable energy solutions. A batch anaerobic digestion process was employed using a 1 L jacketed glass digester, simulating small-scale conditions, while technoeconomic feasibility was projected onto a 500 L digester operated without temperature control, reflecting realistic constraints for decentralized rural or residential systems. Three feedstock mixtures (100% FW, 50:50 FW:CD, and 50:25:25 FW:CD:GW) were tested to determine their impact on biogas yield and methane concentration. Experiments were conducted over 14 days, during which biogas production and methane content were monitored. The results showed that FW alone produced the highest biogas volume, but with a low methane concentration of 25%. Co-digestion with CD and GW enhanced methane quality, achieving a methane yield of 48% while stabilizing the digestion process. A technoeconomic analysis was conducted based on the experimental results to estimate the viability of a 500 L biodigester for small-scale use. The evaluation considered costs, benefits, and financial metrics, including Net Present Value (NPV), Internal Rate of Return (IRR), and Dynamic Payback Period (DPP). The biodigester demonstrated strong economic potential, with an NPV of AUD 2834, an IRR of 13.5%, and a payback period of 3.2 years. This study highlights the significance of optimizing feedstock composition and integrating economic assessments with experimental findings to support the adoption of biogas systems as a sustainable energy solution for small-scale, off-grid, or rural applications. Full article
(This article belongs to the Special Issue Biomass and Bio-Energy—2nd Edition)
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14 pages, 20914 KB  
Article
Effect of the Non-Magnetic Ion Doping on the Magnetic Behavior of MgCr2O4
by Fuxi Zhou, Zheng He, Donger Cheng, Han Ge, Wenjing Zhang, Xiao Wang, Pengfei Zhou, Wanju Luo, Zhengdong Fu, Xinzhi Liu, Liusuo Wu, Lunhua He, Yanchun Zhao and Erxi Feng
Magnetism 2025, 5(3), 19; https://doi.org/10.3390/magnetism5030019 (registering DOI) - 25 Aug 2025
Abstract
Geometrically frustrated magnets exhibit exotic excitations due to competing interactions between spins. The spinel compound MgCr2O4, a three-dimensional Heisenberg antiferromagnet, hosts both spin-wave and spin-resonance modes, but the origin of its resonant excitations remains debated. Suppressing magnetic order via [...] Read more.
Geometrically frustrated magnets exhibit exotic excitations due to competing interactions between spins. The spinel compound MgCr2O4, a three-dimensional Heisenberg antiferromagnet, hosts both spin-wave and spin-resonance modes, but the origin of its resonant excitations remains debated. Suppressing magnetic order via non-magnetic doping can help isolate these modes in neutron scattering studies. We synthesized Ga3+ and Cd2+-doped MgCr2O4 via solid-state reaction and analyzed their structure and magnetism. Ga3+ doping (0–20%) causes anomalous lattice shrinkage due to site disorder from Ga3+ occupying both Mg2+ and Cr3+ sites. Magnetically, Ga3+ doping drives the system from the antiferromagnetic order to a spin-glass state, fully suppressing magnetic ordering at 20% doping. In contrast, Cd2+ replaces only Mg2+, expanding the lattice and meantime inducing strong spin-glass behavior. At 10% Cd2+, long-range antiferromagnetic order is entirely suppressed. Thus, 10% Cd-doped MgCr2O4 offers an ideal platform to study the resonant magnetic excitations without any spin-wave interference. Full article
(This article belongs to the Special Issue Research on the Magnetism of Heavy-Fermion Systems)
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20 pages, 1853 KB  
Article
CRISPR/Cas9 TCR-Edited NKp30 CAR T Cells Exhibit Superior Anti-Tumor Immunity to B7H6-Expressing Leukemia and Melanoma
by Sedigheh Givi, Benedikt J. Lohnes, Saber Ebrahimi, Sophie Riedel, Sneha Khokhali, Shamsul A. Khan, Maximilian Keller, Catherine Wölfel, Hakim Echchannaoui, Ernesto Bockamp, Maya C. Andre, Hinrich Abken, Matthias Theobald and Udo F. Hartwig
Int. J. Mol. Sci. 2025, 26(17), 8235; https://doi.org/10.3390/ijms26178235 (registering DOI) - 25 Aug 2025
Abstract
Chimeric antigen receptor (CAR) T-cell therapy directed to CD19 and B-cell maturation antigen has revolutionized treatment of B-cell leukemia and lymphoma, and multiple myeloma. However, identifying suitable targets for acute myeloid leukemia (AML) remains challenging due to concurrent expression of potential target antigens [...] Read more.
Chimeric antigen receptor (CAR) T-cell therapy directed to CD19 and B-cell maturation antigen has revolutionized treatment of B-cell leukemia and lymphoma, and multiple myeloma. However, identifying suitable targets for acute myeloid leukemia (AML) remains challenging due to concurrent expression of potential target antigens on normal hematopoietic stem cells or tissues. As the stress-induced B7H6 molecule is rarely found on normal tissues but expressed on many cancers including AML and melanoma, the NKp30-ligand B7H6 emerges as a promising target for NKp30-based CAR T therapy for these tumors. In this study, we report a comprehensive B7H6 expression analysis on primary AML and melanoma as well as on different tumor cell-lines examined by RT-qPCR and flow cytometry, and efficient anti-tumor reactivity of NKp30-CAR T cells to AML and melanoma. To overcome limitations of autologous CAR T-cell fitness-dependent efficacy and patient-tailored production, we generated CRISPR/Cas9-mediated TCR-knockout (TCRKO) NKp30-CAR T cells as an off-the-shelf approach for CAR T therapy. Functional studies comparing NKp30-CD28 CAR or NKp30-CD137 CAR TCR+ and TCRKO T lymphocytes revealed superior anti-tumoral immunity of NKp30-CD28 CAR TCRKO T cells to AML and melanoma cell lines in vitro, and effective control of tumor burden in an NSG melanoma-xenograft mouse model. In conclusion, these findings highlight the therapeutic potential of NKp30 CAR TCRKO T cells for adoptive T-cell therapy to B7H6-expressing cancers, including melanoma and AML. Full article
(This article belongs to the Special Issue Advanced Research on CAR-T Cell Therapy)
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20 pages, 907 KB  
Review
Cirrhotic Cardiomyopathy: Bridging Hepatic and Cardiac Pathophysiology in the Modern Era
by Dragoș Lupu, Camelia Cornelia Scârneciu, Diana Țînț and Cristina Tudoran
J. Clin. Med. 2025, 14(17), 5993; https://doi.org/10.3390/jcm14175993 (registering DOI) - 25 Aug 2025
Abstract
Cirrhotic cardiomyopathy (CCM) is a cardiac dysfunction in patients with cirrhosis, occurring in the absence of structural heart disease. It increases perioperative risk, especially in liver transplantation, and may contribute to hepatorenal syndrome. Despite its clinical significance, CCM remains poorly understood and lacks [...] Read more.
Cirrhotic cardiomyopathy (CCM) is a cardiac dysfunction in patients with cirrhosis, occurring in the absence of structural heart disease. It increases perioperative risk, especially in liver transplantation, and may contribute to hepatorenal syndrome. Despite its clinical significance, CCM remains poorly understood and lacks effective treatments. This review aims to summarize recent findings on the pathogenesis of CCM and highlight potential therapeutic targets. A focused literature review was conducted using PubMed, Scopus, and Clarivate databases, selecting studies from the last five years. Included studies investigated molecular, cellular, and receptor-mediated mechanisms involved in CCM. Results: CCM results from neurohumoral, inflammatory, and electrophysiological disturbances. Key mechanisms involve dysfunction of β-adrenergic and muscarinic receptors, altered ion channels (potassium, L-type calcium), impaired sodium–calcium exchange, and suppression of the P2X7 receptor (P2X7R). Dysregulation of the CD73 (5’-nucleotidase, ecto-5’-nucleotidase)–A2 adenosine axis, along with effects from endocannabinoids, nitric oxide (NO) inhibition by tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), carbon monoxide (CO), and elevated galectin-3 (Gal-3), further contribute to myocardial dysfunction. Conclusions: CCM is a multifactorial condition linked to systemic and myocardial effects of cirrhosis. A deeper understanding of its mechanisms is essential for developing targeted therapies. Further research is needed to improve patient outcomes. Full article
(This article belongs to the Special Issue Clinical Management of Patients with Heart Failure—2nd Edition)
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35 pages, 11851 KB  
Article
Numerical Investigation of Concave-to-Convex Blade Profile Transformation in Vertical Axis Wind Turbines for Enhanced Performance Under Low Reynolds Number Conditions
by Venkatesh Subramanian, Venkatesan Sorakka Ponnappa, Madhan Kumar Gurusamy and Kadhavoor R. Karthikeyan
Fluids 2025, 10(9), 221; https://doi.org/10.3390/fluids10090221 - 25 Aug 2025
Abstract
Vertical axis wind turbines (VAWTs) are increasingly utilized for decentralized power generation in urban and low-wind settings because of their omnidirectional wind capture and compact form. This study numerically investigates the aerodynamic performance of Darrieus-type VAWT blades as their curvature varies systematically from [...] Read more.
Vertical axis wind turbines (VAWTs) are increasingly utilized for decentralized power generation in urban and low-wind settings because of their omnidirectional wind capture and compact form. This study numerically investigates the aerodynamic performance of Darrieus-type VAWT blades as their curvature varies systematically from deeply convex (−50 mm) to strongly concave (+50 mm) across seven configurations. Using steady-state computational fluid dynamics (CFD) with the frozen rotor method, simulations were conducted over a low Reynolds number range of 25 to 300, representative of small-scale and rooftop wind scenarios. The results indicate that deeply convex blades achieve the highest lift-to-drag ratio (Cl/Cd), peaking at 1.65 at Re = 25 and decreasing to 0.76 at Re = 300, whereas strongly concave blades show lower and more stable values ranging from 0.95 to 0.86. The power coefficient (Cp) and torque coefficient (Ct) similarly favor convex shapes, with Cp starting at 0.040 and remaining above 0.030, and Ct sustaining a robust 0.067 at low Re. Convex blades also maintain higher tip speed ratios (TSR), exceeding 1.30 at Re = 300. Velocity and pressure analyses reveal that convex profiles promote stable laminar flows and compact wakes, whereas concave geometries experience early flow separation and fluctuating torque. These findings demonstrate that optimizing the blade curvature toward convexity enhances the start-up, torque stability, and power output, providing essential design guidance for urban VAWTs operating under low Reynolds number conditions. Full article
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16 pages, 2673 KB  
Article
Immunogenic Responses Elicited by a Pool of Recombinant Lactiplantibacillus plantarum NC8 Strains Surface-Displaying Diverse African Swine Fever Antigens Administered via Different Immunization Routes in a Mouse Model
by Assad Moon, Hongxia Wu, Tao Wang, Lian-Feng Li, Yongfeng Li, Zhiqiang Xu, Jia Li, Yanjin Wang, Jingshan Huang, Tianqi Gao, Yuan Sun and Hua-Ji Qiu
Vaccines 2025, 13(9), 897; https://doi.org/10.3390/vaccines13090897 - 25 Aug 2025
Abstract
Background: African swine fever (ASF) is a highly contagious and often deadly disease that poses a major threat to swine production worldwide. The lack of a commercially available vaccine underscores the critical need for innovative immunization strategies to combat ASF. Methods: Six ASFV [...] Read more.
Background: African swine fever (ASF) is a highly contagious and often deadly disease that poses a major threat to swine production worldwide. The lack of a commercially available vaccine underscores the critical need for innovative immunization strategies to combat ASF. Methods: Six ASFV antigenic proteins (K78R, A104R, E120R, E183L, D117L, and H171R) were fused with the Lactiplantibacillus plantarum WCFS1 surface anchor LP3065 (LPxTG motif) to generate recombinant Lactiplantibacillus plantarum NC8 (rNC8) strains. The surface expression was confirmed using immunofluorescence and Western blotting assays. Additionally, the dendritic cell-targeting peptides (DCpep) were co-expressed with each antigen protein. Mice were immunized at a dosage of 109 colony-forming units (CFU) per strain per mouse via intragastric (I.G.), intranasal (I.N.), and intravenous (I.V.) routes. The bacterial mixture was heat-inactivated by boiling for 15 min to destroy viable cells while preserving antigenic structures. I.V. administration caused no hypersensitivity, confirming the method’s safety and effectiveness. Results: Following I.G. administration, rNC8-E120R, rNC8-E183L, rNC8-K78R, and rNC8-A104R induced significant levels of secretory immunoglobulin A (sIgA) in fecal samples, whereas rNC8-H171R and rNC8-D117L failed to induce a comparable response. Meanwhile, rNC8-D117L, rNC8-K78R, and rNC8-A104R also elicited significant levels of sIgA in bronchoalveolar lavage fluid (BALF). Following I.N. immunization, rNC8-E120R, rNC8-K78R, and rNC8-A104R significantly increased sIgA levels in both fecal and BALF immunization. In contrast, I.V. immunization with heat-inactivated rNC8-K78R and rNC8-A104R induced robust serum IgG titers, whereas the remaining antigens elicited minimal or insignificant responses. Flow cytometry analysis revealed expanded CD3+CD4+ T cells in mice immunized via the I.N. and I.G. and CD3+CD4+ T cells only in those immunized via the I.N. route. Th1 responses were also significant in the sera of mice immunized via the I.G. and I.N. routes. Conclusions: The rNC8 multiple-antigen cocktail elicited strong systemic and mucosal immune responses, providing a solid foundation for the development of a probiotic-based vaccine against ASF. Full article
(This article belongs to the Special Issue Vaccines for Porcine Viruses)
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13 pages, 803 KB  
Communication
Sex-Specific Differences in Adipose IRF5 Expression and Its Association with Inflammation and Insulin Resistance in Obesity
by Shihab Kochumon, Noelle Benobaid, Ashraf Al Madhoun, Shaima Albeloushi, Nourah Almansour, Fatema Al-Rashed, Sardar Sindhu, Fahd Al-Mulla and Rasheed Ahmad
Int. J. Mol. Sci. 2025, 26(17), 8229; https://doi.org/10.3390/ijms26178229 - 25 Aug 2025
Abstract
Interferon regulatory factor 5 (IRF5) plays a pivotal role in innate immune responses and macrophage polarization. Although its role in obesity-associated inflammation has been described, sex-specific differences in adipose IRF5 expression and its association with immune and metabolic markers remain poorly defined. To [...] Read more.
Interferon regulatory factor 5 (IRF5) plays a pivotal role in innate immune responses and macrophage polarization. Although its role in obesity-associated inflammation has been described, sex-specific differences in adipose IRF5 expression and its association with immune and metabolic markers remain poorly defined. To evaluate sex-specific associations between adipose tissue (AT) IRF5 expression and key inflammatory and metabolic markers in overweight and obese individuals. Subcutaneous AT samples from overweight/obese male and female subjects were analyzed for IRF5 expression using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Correlation and multiple linear regression analyses were performed to identify its associations with inflammatory gene expression and metabolic parameters including insulin, glucose, HOMA-IR, and adipokines. RF5 gene and protein levels were significantly elevated in the AT of overweight/obese females compared to males (p < 0.0001), with expression increasing progressively with BMI in females but not in males. Despite these sex-dependent expression levels, IRF5 demonstrated consistent, sex-independent positive correlations with several core immune and inflammatory markers, including CCR5, CD11c, CD16, CD163, FOXP3, RUNX1, and MyD88. However, distinct sex-specific patterns emerged: in males, IRF5 correlated positively with classical pro-inflammatory markers such as IL-2, IL-6, IL-8, TNF-α, and IRAK1; whereas in females, IRF5 was associated with a broader array of immune markers, including chemokines (CCL7, CXCL11), pattern recognition receptors (TLR2, TLR8, TLR9), and macrophage markers (CD68, CD86), along with anti-inflammatory mediators such as IL-10 and IRF4. Notably, IRF5 expression in overweight/obese males, but not females, was significantly associated with metabolic dysfunction, showing positive correlations with fasting blood glucose, HbA1c, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) levels. Multiple regression analyses revealed sex-specific predictors of IRF5 expression, with metabolic (HOMA-IR) and inflammatory (IRAK1, MyD88) markers emerging in males, while immune-related genes (RUNX1, CD68, CCL7, MyD88) predominated in females. These findings underscore a sex-divergent role of IRF5 in AT, with implications for differential regulation of immune-metabolic pathways in obesity and its complications. Full article
(This article belongs to the Section Molecular Immunology)
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34 pages, 1060 KB  
Review
Beyond the Biomarker: Monomeric CRP as a Driver of Multisystem Pathology in Rheumatoid Arthritis
by Andreea Lazarut-Nistor and Mark Slevin
Int. J. Mol. Sci. 2025, 26(17), 8227; https://doi.org/10.3390/ijms26178227 - 25 Aug 2025
Abstract
Chronic inflammation underpins the pathogenesis of both rheumatoid arthritis (RA) and neurodegenerative conditions such as Alzheimer’s disease (AD). This narrative review explores the role of C-reactive protein (CRP), particularly its monomeric form (mCRP), as a central molecular link connecting systemic autoimmune inflammation with [...] Read more.
Chronic inflammation underpins the pathogenesis of both rheumatoid arthritis (RA) and neurodegenerative conditions such as Alzheimer’s disease (AD). This narrative review explores the role of C-reactive protein (CRP), particularly its monomeric form (mCRP), as a central molecular link connecting systemic autoimmune inflammation with neuroinflammatory and vascular pathology. In RA, fibroblast-like synoviocytes (FLSs) are activated by CRP through CD32/CD64-mediated signaling, triggering proinflammatory cascades involving NF-κB and p38 MAPK. Recent studies have highlighted that locally synthesized CRP within the synovium may convert to mCRP, amplifying inflammation and tissue damage. Beyond RA, mCRP has been identified within amyloid-beta (Aβ) plaques in AD brains, suggesting a direct role in neurodegenerative pathology. Experimental models also demonstrate that mCRP is upregulated in stroke-affected brain regions and associated with complement activation and blood–brain barrier (BBB) disruption, which is central to AD progression. The convergence of pathways involving IL-6, RAGE (receptor for advanced glycation end-products), and mCRP-mediated complement activation reveals a shared axis of inflammation between RA and AD. This highlights the potential of mCRP not only as a biomarker of chronic inflammation but also as a therapeutic target. Furthermore, evidence from periodontal disease and cardiovascular comorbidities highlights the systemic nature of mCRP-driven inflammation, offering insights into the mechanisms of disease overlap. This review advocates for further mechanistic studies into mCRP signaling, particularly its role at the interface of systemic and neuroinflammation, with the goal of identifying new interventional strategies for patients with RA at elevated risk of neurodegenerative and vascular complications. Full article
(This article belongs to the Special Issue Forward in Vasculitis: Genetics and Beyond)
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25 pages, 1484 KB  
Review
Expression of CD44 and Its Spliced Variants: Innate and Inducible Roles in Nervous Tissue Cells and Their Environment
by Maria Concetta Geloso, Francesco Ria, Valentina Corvino and Gabriele Di Sante
Int. J. Mol. Sci. 2025, 26(17), 8223; https://doi.org/10.3390/ijms26178223 - 24 Aug 2025
Abstract
CD44, a structurally diverse cell-surface glycoprotein, plays a multifaceted and indispensable role in neural tissue across both physiological and pathological conditions. It orchestrates complex cell–extracellular matrix interactions and intracellular signaling through its variant isoforms and post-translational modifications and is broadly expressed in neural [...] Read more.
CD44, a structurally diverse cell-surface glycoprotein, plays a multifaceted and indispensable role in neural tissue across both physiological and pathological conditions. It orchestrates complex cell–extracellular matrix interactions and intracellular signaling through its variant isoforms and post-translational modifications and is broadly expressed in neural stem/progenitor cells, microglia, astrocytes, and selected neuronal populations. The interactions of CD44 with ligands such as hyaluronan and osteopontin regulate critical cellular functions, including migration, differentiation, inflammation, and synaptic plasticity. In microglia and macrophages, CD44 mediates immune signaling and phagocytic activity, and it is dynamically upregulated in neuroinflammatory diseases, particularly through pathways involving Toll-like receptor 4. CD44 expression in astrocytes is abundant during central nervous system development and in diseases, contributing to glial differentiation, reactive astrogliosis, and scar formation. Though its expression is less prominent in mature neurons, CD44 supports neural plasticity, circuit organization, and injury-induced repair mechanisms. Additionally, its expression at nervous system barriers, such as the blood–brain barrier, underscores its role in regulating vascular permeability during inflammation and ischemia. Collectively, CD44 emerges as a critical integrator of neural cell function and intercellular communication. Although the roles of CD44 in glial cells appear to be similar to those explored in other tissues, the expression of this molecule and its variants on neurons reveals peculiar functions. Elucidating the cell-type-specific roles and regulation of CD44 variants may offer novel therapeutic strategies for diverse neurological disorders. Full article
(This article belongs to the Collection Feature Papers in Molecular Neurobiology)
20 pages, 2393 KB  
Article
α-Cyclodextrin/Moringin Impacts Actin Cytoskeleton Dynamics with Potential Implications for Synaptic Organization: A Preliminary Transcriptomic Study in NSC-34 Motor Neurons
by Agnese Gugliandolo, Luigi Chiricosta, Gabriella Calì, Patrick Rollin, Daniele Perenzoni, Renato Iori, Emanuela Mazzon and Simone D’Angiolini
Int. J. Mol. Sci. 2025, 26(17), 8220; https://doi.org/10.3390/ijms26178220 - 24 Aug 2025
Abstract
α-Cyclodextrin/Moringin (α-CD/MOR) is an isothiocyanate showing neuroprotective and antioxidant properties. In this work, we studied in differentiated NSC-34 motor neurons cell line the molecular pathways activated following a treatment of 96 h with α-CD/MOR at different doses, namely 0.5, 5 and 10 μM. [...] Read more.
α-Cyclodextrin/Moringin (α-CD/MOR) is an isothiocyanate showing neuroprotective and antioxidant properties. In this work, we studied in differentiated NSC-34 motor neurons cell line the molecular pathways activated following a treatment of 96 h with α-CD/MOR at different doses, namely 0.5, 5 and 10 μM. Taking advantage of comparative transcriptomic analysis, we retrieved the differentially expressed genes (DEGs) and we mapped DEGs to synaptic genes using the SynGO database. Then, we focused on the biological pathways in which they are involved. We observed that the prolonged treatment with α-CD/MOR significantly modulated biological processes and cellular components associated with synaptic organization. Interestingly, the KEGG pathway “Regulation of actin cytoskeleton” was overrepresented, alongside pathways related to synapses and axon guidance. Specifically, SPIA analysis indicated that the “Regulation of actin cytoskeleton” pathway was found to be activated with the highest dose of α-CD/MOR. Moreover, α-CD/MOR also modulated transcription factors involved in synaptic plasticity, such as Creb1. These results could indicate that α-CD/MOR can influence synaptic functions and organization, being involved in synaptic plasticity through the modulation of actin dynamics. Full article
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