Search Results (32,501)

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative form of immunotherapy, enabling the precise engineering of T cells to recognize and eliminate pathogenic cells. In hematologic malignancies, CAR-T cells targeting CD19 or B cell maturation antigens have achieved remarkable remission rates and durable responses in patients with otherwise refractory disease. Despite these successes, extending CAR-T cell therapy to solid tumors remains challenging due to antigen heterogeneity, poor T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Beyond oncology, CAR-T cell therapy has also shown promise in autoimmune diseases, where early clinical studies suggest that B cell-directed CAR-T cells can induce sustained remission in conditions such as systemic lupus erythematosus. This review highlights advances in CAR-T cell engineering, including DNA- and mRNA-based platforms for ex vivo and in vivo programming, and discusses emerging strategies to enhance CAR-T cell trafficking, persistence, and resistance to TME. Full article

Rapid urbanization in China has driven annual food waste production to 130 million tons, posing severe environmental challenges for anaerobic digestate management. To resolve trade-offs among drying efficiency, resource recovery (fertilizer/fuel), and carbon neutrality by optimizing the biodried product (BDP) recycling ratio (0–15%), six BDP treatments were tested in 60 L bioreactors. Metrics included drying kinetics, product properties, and environmental–economic trade-offs. The results showed that 12% BDP achieved a peak temperature integral (514.13 °C·d), an optimal biodrying index (3.67), and shortened the cycle to 12 days. Furthermore, 12% BDP yielded total nutrients (N + P₂O₅ + K₂O) of 4.19%, meeting the NY 525-2021 standard in China, while ≤3% BDP maximized fuel suitability with LHV > 5000 kJ·kg⁻¹, compliant with CEN/TC 343 RDF standards. BDP recycling reduced global warming potential by 27.3% and eliminated leachate generation, mitigating groundwater contamination risks. The RDF pathway (12% BDP) achieved the highest NPV (USD 716,725), whereas organic fertilizer required farmland subsidies (28.57/ton) to offset its low market value. A 12% BDP recycling ratio optimally balances technical feasibility, environmental safety, and economic returns, offering a closed-loop solution for global food waste valorization. Full article

Background: KMT2A partial tandem duplication (PTD) occurs in approximately 5–10% of acute myeloid leukemia (AML) cases and is associated with poor prognosis. While its cytogenetic and molecular features are well described, the immunophenotypic characteristics of AML with KMT2A-PTD remain incompletely defined. Methods: We identified 47 cases of AML with KMT2A-PTD by optical genome mapping. All cases underwent flow cytometric immunophenotypic analysis and next-generation sequencing using an 81-gene panel. Results: The cohort included 32 men and 15 women with a median age of 67 years (range, 19–87). Thirty-eight cases were de novo AML, and nine were secondary to myelodysplastic syndrome and/or myeloproliferative neoplasm. Most cases (93%) demonstrated a normal or non-complex karyotype. The most frequent mutations involved FLT3-ITD (47%), DNMT3A (43%), and RUNX1 (23%). Thirty-one cases (66%) were granulocytic, while 16 (34%) showed granulocytic and/or monocytic differentiation. Blasts uniformly expressed HLA-DR and frequently expressed CD117 (91%) and CD34 (79%). Increased expression of CD123 (74%) and CD117 (43%) and decreased expression of HLA-DR (74%) and CD38 (69%) were common. Aberrant CD25 expression was observed in 51% of cases. Increased CD123 and aberrant CD25 expression were significantly associated with FLT3-ITD mutations (both p < 0.0001) but not with other recurrent mutations. There was no correlation between FLT3-ITD mutation and expression levels of CD117, CD38 or HLA-DR (all p > 0.05). Conclusions: AML with KMT2A-PTD shows distinctive immunophenotypic features with increased CD123 and aberrant CD25 expression, both associated with FLT3-ITD. These markers may have diagnostic and therapeutic relevance in this AML subtype. Full article

Background/Objectives: Essential oils (EOs) from plants of the genus Cinnamomum have been widely used based on their antimicrobial, antioxidant, and anti-inflammatory properties. However, their elevated volatility and limited aqueous solubility restrict their use in pharmaceutical and food formulations. Cyclodextrins (CDs) have emerged as a promising strategy to overcome these limitations through the formation of inclusion complexes. Methods: In this study, inclusion complexes of essential oil from C. camphora L. (EOCNM) with β-cyclodextrin (β-CD) were developed using physical mixing (PM), ultrasonic treatment (US), and freeze-drying (FD). The inclusion complexes were physicochemically characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TG/DTG), X-ray diffraction (XRD), and scanning electron microscopy (SEM) to evaluate their physicochemical interactions and complexation efficiency. Results: Our results demonstrated successful complex formation, with the FD and US methods showing greater amorphization and stronger inclusion characteristics compared to the PM method. Thermal analysis confirmed improved physicochemical stability of the essential oil when complexed with β-CD. Furthermore, the cytotoxicity assay of the complexes was assessed using the MTT assay and J774 macrophage cells. The complexes exhibited low cytotoxicity, indicating their potential biocompatibility for biomedical and food applications. Conclusions: Overall, β-CD encapsulation effectively enhanced the physicochemical stability and safety profile of C. camphora essential oil, providing a promising strategy for its controlled delivery and protection against degradation. Full article

A multifunctional diagnosis and treatment carrier, ZIF-8@CDs, based on carbon quantum dots (CDs) and the zeolitic imidazolate framework-8 (ZIF-8) metal–organic framework which serves as a core structure for constructing the responsive delivery platform, is developed in this paper. The anticancer drug doxorubicin (DOX) and Survivin oligo (siRNA) are loaded to form a ZIF-8@CDs/DOX@siRNA dual loading platform. CDs of 5–10 nm are synthesized by the solvent method and combined with ZIF-8. Electron microscopy shows that the composites are nearly spherical particles of approximately 200 nm, and the surface potential decreases from +36 mV before loading CDs to +25.7 mV after loading. The composite system shows unique advantages: (1) It has Fenton-like catalytic activity, catalyzes H₂O₂ to generate hydroxyl radicals, and consumes glutathione in the tumor microenvironment. The level of reactive oxygen species (ROS) in the ZIF-8@CDs group is significantly higher than that in the control group. (2) To achieve visual diagnosis and treatment, its fluorescence intensity is superior to that of the traditional Fluorescein isothiocyanate (FITC)-labeled vector; (3) It has a high loading capacity, with the loading amount of small nucleic acids reaching 36.25 μg/mg, and the uptake rate of siRNA by liver cancer cells is relatively ideal. The ZIF-8@CDs/DOX@siRNA dual-loading system is further constructed. Flow cytometry shows that the apoptosis rate of HepG2 cells induced by the ZIF-8@CDs/DOX@siRNA dual-loading system is 49%, which is significantly higher than that of the single-loading system (ZIF-8@CDs/DOX: 34.3%, ZIF-8@CDs@siRNA: 24.2%) and the blank vector (ZIF-8@CDs: 12.6%). The platform provides a new strategy for the integration of tumor diagnosis and treatment through the multi-mechanism synergy of chemical kinetic therapy, gene silencing and chemotherapy. Full article

Myelodysplastic syndromes/neoplasms (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and a variable risk of progression to secondary acute myeloid leukemia (sAML). Despite major advances in the molecular and clinical characterization of MDS, mechanistic and translational research remains constrained by the limited availability of well-validated in vitro models. Many historically used cell lines are difficult to maintain, exhibit restricted proliferative capacity, or represent advanced disease stages rather than bona fide MDS, while others have been affected by misidentification or cross-contamination. This review provides a comprehensive and critical overview of currently available MDS and MDS-related cell lines, including MDS92, MDS-L and its sublines, M-TAT, TER-3, SKK-1, SKM-1, and MOLM-17/18. We summarize their clinical origin, cytogenetic and molecular features, growth factor dependence, differentiation capacity, and experimental applications, with particular emphasis on their relevance to disease stage, clonal evolution, and leukemic transformation. In addition, we discuss the controversy surrounding misidentified models such as PC-MDS and highlight the importance of rigorous cell line authentication. Full article

Leccinum is an ecologically significant and taxonomically complex genus of ectomycorrhizal fungi widely distributed across boreal, temperate, Mediterranean, and selected tropical regions. Despite its ecological, nutritional, and applied importance, no comprehensive review has previously synthesized global knowledge on this genus. This work provides the first integrative assessment of Leccinum research, combining a bibliometric analysis of 293 peer-reviewed publications with an in-depth qualitative synthesis of ecological, biochemical, and environmental findings. Bibliometric results show increasing scientific attention since the mid-20th century, with major contributions from Europe, Asia, and North America, and dominant research themes spanning taxonomy, ecology, chemistry, and environmental sciences. The literature review highlights substantial advances in phylogenetic understanding, species diversity, and host specificity. Leccinum forms ectomycorrhizal associations with over 60 woody host genera, underscoring its functional importance in forest ecosystems. Nutritionally, Leccinum species are rich in proteins, carbohydrates, minerals, bioactive polysaccharides, phenolic compounds, and umami-related peptides, with demonstrated antioxidant, immunomodulatory, and antitumor activities. At the same time, the genus exhibits notable bioaccumulation capacity for heavy metals (particularly Hg, Cd, and Pb) and radionuclides, making it both a valuable food source and a sensitive environmental bioindicator. Applications in biotechnology, environmental remediation, forest restoration, and functional food development are emerging but remain insufficiently explored. Identified research gaps include the need for global-scale phylogenomic frameworks, expanded geographic sampling, standardized biochemical analyses, and deeper investigation into physiological mechanisms and applied uses. This review provides the first holistic synthesis of Leccinum, offering an integrated perspective on its taxonomy, ecology, nutritional composition, environmental significance, and practical applications. The findings serve as a foundation for future mycological, ecological, and biotechnological research on this diverse and understudied fungal genus. Full article

Although the SARS-CoV-2 pandemic no longer poses a global emergency, the virus continues to diversify and acquire immunoevasive properties. Understanding the molecular pathways that shape SARS-CoV-2 pathogenesis has become essential. In this paper, we summarize the most recent current evidence on how the spike protein structurally evolves, on changes in key non-structural proteins, such as nsp14, and on host factors, such as TMPRSS2 and neuropilin-1. These changes, together, shape viral entry, replication fidelity and interferon antagonism. Given the emerging Omicron variants of SARS-CoV-2, recent articles in the literature, cryo-EM analyses, and artificial intelligence-assisted mutational modeling were analyzed to infer and contextualize mutation-driven mechanisms. It is through these changes that the virus adapts and evolves, such as optimizing angiotensin-converting enzyme binding, modifying antigenic surfaces, and accumulating mutations that affect CD8⁺ T-cell recognition. Multi-omics data studies further support SARS-CoV-2 pathogenesis through convergent evidence linking viral adaptation to host immune and metabolic reprogramming, as occurs in myocarditis, liver injury, and acute kidney injury. By integrating proteomic, transcriptomic, and structural findings, this work presents how the virus persists and dictates disease severity through interferon antagonism (ORF6, ORF9b, and nsp1), adaptive immune evasion, and metabolic rewiring. All these insights underscore the need for next-generation interventions that provide a multidimensional framework for understanding the evolution of SARS-CoV-2 and guiding future antiviral strategies. Full article

Neuronal synapses are the functional units of communication in the central nervous system. This review describes the molecular mechanisms regulating synaptic transmission, plasticity, and circuit refinement. At the presynaptic active zone, scaffolding proteins including bassoon, piccolo, RIMs, and munc13 organize vesicle priming and the localization of voltage-gated calcium channels. Neurotransmitter release is mediated by the SNARE complex, comprising syntaxin-1, SNAP25, and synaptobrevin, and triggered by the calcium sensor synaptotagmin-1. Following exocytosis, synaptic vesicles are recovered through clathrin-mediated, ultrafast, bulk, or kiss-and-run endocytic pathways. Postsynaptically, the postsynaptic density (PSD) serves as a protein hub where scaffolds such as PSD-95, shank, homer, and gephyrin anchor excitatory (AMPA, NMDA) and inhibitory (GABA-A, Glycine) receptors are observed. Synaptic strength is modified during long-term potentiation (LTP) and depression (LTD) through signaling cascades involving kinases like CaMKII, PKA, and PKC, or phosphatases such as PP1 and calcineurin. These pathways regulate receptor trafficking, Arc-mediated endocytosis, and actin-dependent remodeling of dendritic spines. Additionally, synapse formation and elimination are guided by cell adhesion molecules, including neurexins and neuroligins, and by microglial pruning via the complement cascade (C1q, C3) and “don’t eat me” signals like CD47. Molecular diversity is further expanded by alternative splicing and post-translational modifications. A unified model of synaptic homeostasis is required to understand the basis of neuropsychiatric and neurological disorders. Full article

Inflammatory Bowel Diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated disorders marked by persistent and recurrent inflammation of the gastrointestinal tract. Over the past two decades, major advances in understanding the immunologic and molecular pathways that drive intestinal injury have transformed the therapeutic landscape. This progress has enabled the development of novel biologics and small-molecule agents that more precisely target dysregulated immune responses, thereby improving clinical outcomes and quality of life for many patients. Despite these therapeutic advances, IBD remains a highly heterogeneous condition. Patients differ widely in disease phenotype, progression, and response to specific treatments. Consequently, selecting the most effective therapy for an individual patient requires careful consideration of clinical features, molecular markers, and prior treatment history. The shift toward personalized, prediction-based treatment strategies aims to optimize the timing and choice of therapy, minimize unnecessary exposure to ineffective drugs, and ultimately alter the natural course of disease. In this review, we provide a comprehensive overview of current evidence guiding drug positioning in IBD, with particular emphasis on biologic therapies and small-molecule inhibitors. We also examine emerging biomarkers, clinical predictors of response, and real-world factors that influence therapeutic decision-making. Finally, we discuss the challenges and limitations that continue to hinder widespread implementation of personalized strategies, underscoring the need for further research to integrate precision medicine into routine IBD care. Full article

Trace elements are essential for organisms, and their involvement in diverse diseases is increasingly recognised. Interest is increasing in veterinary medicine, particularly in relation to canine diseases. However, reference intervals for trace elements in dogs remain scarce. Plasma samples from 140 dogs were analysed by inductively coupled plasma mass spectrometry to determine the levels of 13 trace elements. Reference intervals (µg/L) were established for the following 12 elements: As, 0.417–8.17; Co, 0.039–1.33; Cr, 2.41–13.3; Cu, 296–790; Fe, 846–3643; Hg, 0.235–2.33; Ni, 0.567–9.04; Mn, 1.90–7.28; Mo, 1.43–12.7; Pb, 0.285–2.82; Se, 200–434; and Zn, 415–1095. However, Cd was below the limit of quantification in 77% of the samples. No differences in trace element concentrations were observed in relation to breed or reproductive status. Statistically significant differences were found in relation to sex (Cu, Mo, Zn), age (Co, Cu, Mo, Mn, Se, Zn), and size (Cu, Mo, Se, Zn); however, the magnitude of these effects varied among elements and was generally weak. Nevertheless, these factors should be considered when assessing trace element status. These reference intervals constitute an important resource for both clinical evaluation and future research. Full article

Background and Objectives: People living with HIV (PLWH) have excess osteoporosis and fractures not fully captured by dual-energy X-ray absorptiometry (DXA). We evaluated whether trabecular bone score (TBS), calcaneal quantitative ultrasound (QUS) and bone turnover markers improve vertebral fracture risk assessment beyond areal bone mineral density (BMD) in PLWH. Methods: In this cross-sectional study, 87 antiretroviral-treated adults undergoing DXA had lumbar spine TBS and calcaneal QUS. Morphometric vertebral fractures were identified, correlates of degraded TBS were analyzed using multivariable regression, and sequential logistic models quantified the incremental contribution of TBS and CTX to discriminate for prevalent morphometric vertebral fractures. Results: Low BMD (osteopenia/osteoporosis) was present in 62% of participants, degraded TBS in 37% and morphometric vertebral fractures in 17%. Degraded versus normal TBS was associated with older age (49.1 vs. 39.7 years), longer HIV duration and lower nadir CD4+ count, as well as more frequent tenofovir disoproxil fumarate exposure (66% vs. 52%; all p ≤ 0.04). In multivariable analysis, age (per 10-year increase; adjusted odds ratio [aOR] 1.78; 95% CI 1.13–2.83) and nadir CD4+ < 200 cells/mm³ (aOR 2.29; 95% CI 1.06–4.97) independently predicted degraded TBS. In sequential cross-sectional models for prevalent morphometric vertebral fractures, the area under the curve increased from 0.71 (clinical variables) to 0.79 after adding lumbar spine T-score and to 0.85 after adding TBS; adding CTX yielded 0.87 without a statistically significant incremental gain. Conclusions: In PLWH, TBS captures bone quality deficits and improves vertebral fracture risk discrimination beyond BMD, supporting its integration alongside DXA in routine HIV care. Full article

Breast cancer is a heterogeneous disease that exists in multiple subtypes, some of which still lack targeted and effective therapy. A major challenge is to unravel their underlying molecular mechanisms and bring to light novel therapeutic targets. In this study, we investigated the role of WNT-inducible signaling pathway protein 1 (WISP1) matricellular protein in the acquirement of an invasive phenotype by breast cancer cells. To this aim, we treated non-invasive MCF7 cells with WISP1 and assessed the expression levels of macrophage migration inhibitory factor (MIF) and its cellular receptor CD74. Next, we examined the expression of epithelial-to-mesenchymal transition (EMT) markers as well as molecular effectors of the tumor microenvironment, such as CD44, the main hyaluronan receptor that also acts as a co-receptor for MIF, the hyaluronan oncogenic network, and specific matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). The results showed that WISP1 potently induces the expression of MIF cytokine and affects the expression of specific extracellular matrix molecules with established roles in the promotion of malignant properties. Notably, Src kinases and MIF are critically involved in these processes. Collectively, the present study demonstrates for first time a WISP1/Src/MIF axis as well as its ability to induce an invasive phenotype in MCF7 cells and highlights novel cellular and molecular processes involved in the epithelial-to-mesenchymal transition and the development of invasive breast cancer. This suggests that specific cues from the tumor microenvironment can activate a migratory/invasive phenotype in a subpopulation of cells residing within the heterogeneous breast tumor. Full article

Pb²⁺ and Cd²⁺ represent common heavy metal contaminants in aquatic environments, posing significant risks to ecosystem stability and human health. To develop efficient adsorbents for removing Cd²⁺ and Pb²⁺ while achieving resource utilization of industrial by-products (red mud and distiller’s grains), this study synthesized a novel composite biochar—red mud–Lactobacillus plantarum composite biochar (RM)—by immobilizing red mud and Lactobacillus plantarum onto biochar derived from distiller’s grains. The structural and chemical properties of RM were characterized using SEM-EDS, XRD, and FTIR. Batch adsorption experiments were conducted to evaluate the effects of various experimental factors on Cd²⁺ and Pb²⁺ adsorption. The adsorption process was further elucidated through kinetic and isothermal models, revealing that it follows the pseudo-second-order kinetic model. Equilibrium data were best described by the Langmuir model for Cd²⁺ and the Freundlich model for Pb²⁺. The maximum adsorption capacities reached 12.13 mg/g for Cd²⁺ and 130.10 mg/g for Pb²⁺. The primary mechanisms involved in Cd²⁺ and Pb²⁺ adsorption by RM include surface complexation, cation–π interactions, ion exchange, and coprecipitation. These findings demonstrate that RM represents a promising and effective adsorbent for the remediation of heavy metal-contaminated water. Full article