Search Results (33,462)

Chronic diabetic wound remain difficult to heal because persistent inflammation, oxidative stress, and impaired regeneration delay repair, while effective noninvasive options are limited. In this study, graphene-based far-infrared radiation (FIR) therapy was evaluated in a streptozotocin (STZ)-induced diabetic rat full-thickness wound model, and mechanisms were examined in vivo and in vitro. Wound closure was quantified by serial imaging, whereas tissue remodeling and angiogenesis were assessed by H&E and Masson’s trichrome staining and CD34-based analyses. Transcriptomic responses were profiled by RNA sequencing with qRT-PCR validation, immune phenotypes were characterized by immunofluorescence, and high-glucose cell assays were performed. Re-epithelialization, collagen deposition, and neovascularization were quantified histologically. These datasets enabled integrated evaluation of inflammation, oxidative stress, and repair programs over time. Graphene FIR accelerated closure, reaching 83.9% healing by day 14 vs. 66.8% in untreated controls. Treatment was associated with downregulation of Cxcl2/Cxcl3, suppression of M1 polarization with enhanced M2 polarization, and reduced ROS accumulation. Consistently, NF-κB signaling was inhibited, supporting restoration of a pro-regenerative microenvironment. Collectively, graphene FIR represents a promising noninvasive strategy for diabetic wound repair via coordinated immunomodulatory and antioxidant actions. Full article

DRG adhesion is a key pathological feature of failed back surgery syndrome and a major cause of neuropathic pain. DRG, or epidural adhesion, commonly results from spinal surgery, leakage of disk material into the epidural space, or inflammation. To better mimic this clinical condition, we developed a novel and reliable animal model of DRG adhesion-induced neuropathic pain. Using this model, we investigated the therapeutic potential and underlying mechanisms of CLARIX FLO, a sterile, particulate human amniotic membrane and umbilical cord tissue product. Our results demonstrate that CLARIX FLO exerts significant analgesic and anti-inflammatory effects in the DRG adhesion model. The application of CLARIX FLO to the injured DRG markedly attenuated mechanical allodynia. CLARIX FLO treatment also reduced outer sheath thickening, suppressed the inflammatory microenvironment, and decreased hypersensitivity of isolectin B4-positive neurons. Mechanistically, CD44 was identified as a potential downstream mediator of CLARIX FLO. Furthermore, a high dose of HC-HA/PTX3, the key bioactive component of CLARIX FLO, effectively reversed mechanical allodynia and inflammation. Notably, CLARIX FLO inhibited the overexpression of TNF-α and TRPV1 adhering to the DRG. In this study, we demonstrated that CLARIX FLO effectively alleviates DRG adhesion-induced neuropathic pain through a CD44–TRPV1-dependent mechanism. Full article

Background: The treatment of perianal fistulas remains challenging, with low healing and high recurrence rates. Autologous adipose-derived regenerative therapies and platelet-rich plasma (PRP) have emerged as adjuncts to surgical intervention for cryptoglandular and Crohn’s disease (CD)-related perianal fistulas (PAF). This systematic review evaluates the outcomes of these therapies as an add-on to surgical intervention. Methods: A systematic search was conducted in several online databases up to December 2025. Studies with ≥10 patients reporting on the use of intraoperative autologous adipose-derived therapies and/or PRP for the treatment of cryptoglandular or CD-related PAF, and clinical healing rates, were included. Other outcomes comprised radiologic healing (as defined in the study), recurrence rates and complications. The study quality was assessed with the Effective Public Health Practice Tool. Results: In total, 28 studies on individual cases were included (n = 1017 patients, range 10–219) (17 in cryptoglandular PAF, 8 in CD-related PAF and 3 in both entities). A total of 57% of the studies were rated low quality. In cryptoglandular PAF, reported healing rates with adipose-derived therapies ranged from 50% to 90% across studies of low to good methodological quality. For PRP, three of the four randomized trials demonstrated no superiority over standard care. In CD-related PAF, healing rates after treatment with adipose-derived therapies ranged from 40% to 80%. For PRP, three studies, of which two were low quality, reported highly variable healing rates (33–80%). Radiologic healing, reported in 10 studies, ranged from 38 to 76% in cryptoglandular and 33–75% in CD-related PAF. Recurrence rates remained <17% for adipose-derived therapies and <31% following treatment with PRP. Major complications occurred in <15% of the patients. Conclusions: High heterogeneity with regard to fistula complexities, outcome definitions and surgical method was observed in the available studies on autologous add-on therapies. This hinders an overall effectiveness analysis. The promising healing rates, low recurrence rates after healing and low complication rates warrant high-quality trials. Full article

Co-pyrolysis of sludge and plastics has gradually emerged as a crucial technical approach for waste reduction and resource recovery. This study develops high-precision, interpretable prediction models and quantifies the contributions of core risk factors to environmental risks. Based on the experimental datasets from 2015 to 2025, which include operational parameters and eight potential toxic elements (PTEs) with four chemical speciation fractions: acid-soluble/exchangeable (F1), reducible (F2), oxidizable (F3), and residual (F4), we constructed six machine learning models. Based on the experimental datasets from 2015 to 2025, which include operational parameters and eight potential toxic elements (PTEs) chemical speciation (F1–F4), we constructed six machine learning models. Feature importance analysis and Shapley Additive Explanation (SHAP) analysis were employed to identify core risk factors and interpret the model’s decision logic. Results indicate that XGBoost, Random Forest and CatBoost outperform other models, achieving test accuracies of 0.94, 0.92, and 0.90, with weighted F1-Scores of 0.94, 0.92, and 0.90, respectively. Feature importance highlights the most important features for the six different models, with Cd-F4, As-F1, and Cu-F4 contributing most significantly to the model predictions. SHAP analysis quantified the contributions of each feature to the model predictions, verified Cd-F4 as the primary risk discriminant, and further revealed that F1 and F4 of PTEs are key factors in distinguishing risk levels. This study proposes an interpretable machine learning framework, providing a theoretical basis for the optimization of the sludge and plastic co-pyrolysis process and the assessment of potential risks. Full article

Background/Objectives: Point-of-care (PoC) manufactured fresh chimeric antigen receptor (CAR)-T cells are typically formulated in hypothermic preservation formulations (HPFs) and stored under hypothermic conditions (2–8 °C) until administered to the patient. However, in current HPFs the shelf life of fresh CAR-T cells is short (~24–36 h) due to limited CAR-T cell stability, which poses significant time constraints on manufacturing procedures and logistics. The objective of this study was to improve the stability and extend the shelf life of fresh clinical-grade CAR-T cell drug products (DPs). Methods: A novel HPF was developed by supplementing a base HPF with the novel excipient SUL-138, which stabilizes mitochondria during hypothermic storage and subsequent rewarming, alone or in combination with endogenous mitochondrial substrates. This panel of HPFs was first screened for their stability-improving characteristics in the model cell line Jurkat cells. Subsequently, HPFs were assessed for their stability-improving characteristics of clinical-grade CD19 CAR-T cell DPs. Critical quality attributes, including CAR-T cell viability, T-cell differentiation state, exhaustion markers, and functional potency were evaluated in a good manufacturing practice (GMP)-compliant stability study up to 72 h. Results: For Jurkat cells, HPFs supplemented with SUL-138 and a combination of glucose, glutamine, and succinate demonstrated the greatest stability improvement at 2–8 °C, improving cell viability from ~1% to >85% after 72 h. For CAR-T cells, supplementation of HPFs with SUL-138 alone demonstrated the greatest improvement, resulting in a CAR-T cell viability from ~40% to >85% after 72 h of storage at 2–8 °C, while no additional benefits from mitochondrial substrates were observed. The novel HPF did not significantly impact CAR-T cell potency test results, T cell subset distribution, or exhaustion markers compared to control. Conclusions: A novel clinical-grade HPF that significantly improved fresh CAR-T cell stability during hypothermic storage was developed. This novel HPF can aid in the establishment of GMP-compliant and PoC CAR-T cell manufacturing platforms. Full article

The surrounding soil in mining areas generally suffers from severe pollution, characterized primarily by multi-metal contamination, and poses significant challenges in restoration and safe utilization. Therefore, it is urgent to explore low-cost restoration and safe utilization technologies that can achieve simultaneous treatment and utilization. This study selected a typical lead-zinc mining area in eastern Yunnan, China, where there is severe heavy metal pollution. It collected 15 common varieties of castor plants and systematically studied their absorption, accumulation, translocation, and removal characteristics of four heavy metal elements (Cd, Pb, Cu, Zn). The results showed that the heavy metal pollution in the mining area was extremely severe. Castor plants have a strong tolerance to heavy metal stress. There were significant differences in the absorption and accumulation of heavy metals among different castor varieties. The root parts mainly accumulated Pb, the stem parts mainly accumulated Cd, and the seeds had a higher ability to accumulate Cu. In terms of restoration potential, the Tong Castor No. 24, Fen Castor No. 10, and Zi Castor No. 3 plants had relatively large restoration potential. However, considering both biomass and heavy metal removal capacity, Dian Castor No, 2 Zi Castor No. 3, Dian Castor No. 5 plants were more ideal and could be applied in the restoration of heavy metal complex pollution soil in mining areas. Full article

Background/Objectives: Sarcoidosis is a granulomatous disease with no widely accepted circulating biomarkers for routine diagnostics. Soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP), identified through extracellular vesicle proteomics, have been proposed as candidates. We aimed to compare the diagnostic accuracy of serum sCD14 and LBP with the established biomarker soluble interleukin-2 receptor alpha chain (sCD25). Methods: A matched case–control study included 46 newly diagnosed, untreated sarcoidosis patients and 46 age- and sex-matched healthy controls. Serum sCD14, sCD25, and LBP were quantified by ELISA. BMI was included as a covariate in multivariable logistic regression. Diagnostic performance was evaluated by ROC analysis and stepwise AIC model selection. Longitudinal biomarker dynamics were assessed in 32 patients under treatment. Results: sCD25 demonstrated superior diagnostic discrimination (AUC 0.92, 95% CI 0.87–0.98), compared with LBP (AUC 0.71, 95% CI 0.60–0.82) and sCD14 (AUC 0.61, 95% CI 0.49–0.73). In multivariate analysis, only sCD25 (OR per +100 pg/mL: 1.53; p < 0.001) remained an independent predictor of sarcoidosis. Neither LBP nor sCD14 improved model fit. All biomarkers significantly decreased following therapy. Conclusions: Among routinely measurable serum markers, sCD25 outperformed sCD14 and LBP in sarcoidosis diagnosis. Further studies should explore immunometabolic interactions to refine diagnostic algorithms. Full article

Apple pomace represents an important agro-industrial residue with high moisture content and significant environmental burden if improperly managed. This study investigated its thermochemical valorisation into biochar via two processes, followed by comprehensive physicochemical characterization and agronomic evaluation. Elemental analysis revealed carbon enrichment from 47.89% in raw material to 77–78% after the thermal process, evidencing a progressive aromatization. Scanning electron microscopy, Fourier transform infrared spectroscopy, and Raman analysis confirmed a temperature-dependent transition from partially amorphous carbon (400 °C) to more ordered aromatic structures (450 °C), while excessive thermal treatment (550 °C) increased structural defects. ICP-OES revealed an enrichment in thermally stable metals (Fe, Al, Mn) and limited Cd accumulation. Germination assays using Triticum aestivum L. demonstrated that biochar produced at 400 °C significantly improved the germination uniformity and seedling height (14.1 mm), as well as biomass accumulation compared to the control soil sample. The fertilizer addition increased the soluble Na and electrical conductivity (up to 643 µS/cm), potentially inducing transient salinity stress. Soil chemical analysis indicated increased K availability in soils amended with biochar produced at 400 °C, whereas the combination of biochar obtained at 450 °C with fertilizer conducted to elevated concentrations of certain trace metals, mainly Ni and Cr, highlighting the demand for careful monitoring. Overall, the biochar produced at 400 °C yielded to an optimal balance between structural stability, nutrient enrichment, and agronomic performance, evidencing that apple pomace may be a viable feedstock for sustainable biochar production within circular bioeconomy frameworks. Full article

This review classifies plant-derived functional ingredients in pet food according to phytochemical groups and application forms, including direct oral supplementation and incorporation into complete diets. Polyphenols and plant extracts exert prominent antioxidant (singular), anti-inflammatory, immunomodulatory, and microbiome-regulating effects. Microalgae and omega-3 sources support lipid metabolism, cardiovascular function, and skin integrity. Cannabinoids demonstrate dose-dependent responses in dogs, while cats generally tolerate long-term administration and exhibit notable benefits in chronic pain management. Combinations of botanical extracts with complementary bioactives and fermented botanical preparations exhibit multi-target functionality, with dogs showing pronounced biochemical and microbiome modulation, whereas cats display more behavioral and functional improvements. Phytochemicals operate through integrated multi-level regulation, including activation of antioxidant enzymes, modulation of inflammatory cytokines and T-lymphocyte ratios, microbial metabolic shifts toward short-chain fatty acid production, and regulation of lipid metabolism. Dogs demonstrate marked effects on hepatic function, reproductive resilience, microbiome diversity, CD4+/CD8+ balance, and cholesterol control. In contrast, cats show greater benefits in inflammation reduction, pain relief, intestinal integrity, and long-term safety. These species-specific responses underscore the importance of precision formulation and highlight the emergence of plant-based “pharma-pet nutrition” integrating nutritional and biochemical strategies for targeted health promotion. Full article

Background: Short-chain fatty acids (SCFAs) support mucosal integrity and reduce inflammation, while nesfatin-1 is a neuropeptide with antiapoptotic, anti-inflammatory, antioxidant, and anorexigenic actions. Their roles in inflammatory bowel disease (IBD) and links to quality of life (QoL) are unclear. Methods: We conducted a cross-sectional study including adults with Crohn’s disease (CD), ulcerative colitis (UC), and healthy controls (HC). Serum total short-chain fatty acids and nesfatin-1 were measured using enzyme-linked immunosorbent assays (ELISA). Quality of life was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). Group comparisons and correlation analyses were performed using non-parametric statistical methods. Results: Serum total SCFA concentrations did not differ significantly between patients with CD, UC, and HC (p = 0.29). Nesfatin-1 levels showed between-group variability, with lower values in CD compared with healthy controls, while patients with UC showed intermediate and variable levels (p = 0.064). An inverse correlation between SCFAs and nesfatin-1 was observed in UC and in the combined IBD cohort, but not in CD. Quality of life was comparably impaired in CD and UC. No statistically significant associations were observed between serum SCFAs or nesfatin-1 and IBDQ scores. Conclusions: In this pilot exploratory study, circulating SCFAs and nesfatin-1 showed distinct patterns across IBD subtypes, with evidence of subtype-specific associations between these biomarkers. However, no relationship with quality of life was demonstrated. Larger longitudinal studies are required to confirm these findings and clarify their clinical relevance. Full article

To develop high-performance iridium phosphorescent complexes, we designed and synthesized a series of iridium phosphorescent complexes (G-1, G-2, B-1, B-2, R-1, R-2) using 3-hydroxy-2-methyl-4-pyrone (maltol, short for mal) and 3-hydroxy-2-ethyl-4-pyrone (ethyl maltol, short for emal) as auxiliary ligands, in combination with 2-phenylpyridine (ppy), 2-(2,4-difluorophenyl)pyridine (dfppy), and 1-phenylisoquinoline (piq) as cyclometalating ligands. We systematically investigated their crystal structures, photophysical behavior, electrochemical properties, and electroluminescent performance. The results revealed that the combination of a pyranone auxiliary ligand with the highly conjugated piq ligand leads to the formation of R-1 and R-2, which possess high molecular symmetry and display favorable photophysical performance. These complexes exhibit solution-phase phosphorescence quantum yields of 64% and 55%, and electroluminescent devices incorporating them reach a maximum external quantum efficiency of 13.4%, with brightness exceeding 13,000 cd/m² and minimal efficiency roll-off. In contrast, complexes incorporating pyridine-based cyclometalating ligands (ppy, dfppy)—G-1, G-2, B-1, and B-2—display weak emission in solution but show enhanced solid-state emission through π–π stacking, with a maximum quantum yield of 25.8%. Density functional theory calculations and electrochemical analysis indicate that the presence of both the pyranone auxiliary ligand and the piq ligand results in optimized frontier orbital energy alignment, enhanced metal-to-ligand charge transfer, and reduced non-radiative transitions, thereby improving emission efficiency. This study provides a theoretical framework and molecular design strategy for the application of pyranone auxiliary ligands in high-performance iridium phosphorescent materials. Full article

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by profound molecular heterogeneity and high relapse rates, posing significant clinical challenges. Programmed cell death (PCD), encompassing diverse regulated modalities such as apoptosis, necroptosis, and ferroptosis, plays a key role in leukemogenesis and therapeutic response; however, a comprehensive prognostic framework integrating multi-modal PCD pathways in AML remains elusive. In this study, we performed a systematic transcriptomic analysis of 1624 genes associated with 13 distinct PCD forms. A novel computational pipeline combining a variational autoencoder (VAE) for dimensionality reduction and a multilayer perceptron (MLP) for classification was employed to identify robust PCD-related biomarkers, interpreted via SHapley Additive exPlanations (SHAP) analysis. This approach identified 48 candidate genes with discriminative potential between AML and normal bone marrow. Unsupervised consensus clustering based on these genes delineated two molecular subtypes exhibiting divergent clinical outcomes and immune microenvironment profiles. The subtype demonstrated an immunosuppressive phenotype, characterized by enriched regulatory T cells, M2 macrophages, and elevated expression of inhibitory immune checkpoints, correlating with inferior survival. We developed an 8-gene prognostic signature (SORL1, PIK3R5, RIPK3, ELANE, GPX1, VNN1, CD74, and IL3RA) that effectively categorized patients into high- and low-risk groups with notable survival differences, validated across independent cohorts. A prognostic nomogram combining the risk score, age, and cytogenetic risk enhanced the prediction accuracy for overall survival. Our study presents an integrative model that connects multi-modal PCD pathways to AML prognosis, offering a new molecular subtyping system and a clinically applicable risk assessment tool for improved prognostication and personalized treatment strategies. Full article

Background/Objectives: Inflammatory bowel disease (IBD) requires sustained self-care, yet patients’ ability to manage daily treatment and symptoms is often shaped by the support provided by informal caregivers. Methods: Guided by the Middle-Range Theory of Self-Care of Chronic Illness, this multicentre cross-sectional study described caregivers’ contributions to self-care maintenance, monitoring, and management in IBD, and compared these contributions between caregivers of patients with Crohn’s disease (CD) and those of patients with ulcerative colitis (UC). Results: A convenience sample of 275 caregivers of adult outpatients with IBD was recruited across multiple Italian centres. Caregiver contribution was measured using the Caregiver Contribution to Self-Care of Chronic Illness Inventory, together with caregiver self-efficacy and selected sociodemographic and clinical variables. Caregivers reported substantial involvement across all self-care domains, with significantly higher contributions to self-care maintenance among caregivers of patients with CD than among those caring for patients with UC. Monitoring and management scores were similar across groups. Regression analyses indicated disease-specific patterns, with caregiver gender, education, employment status, and patient clinical characteristics showing differential associations with self-care domains. Conclusions: These findings underscore the central role of caregivers in supporting self-care in IBD and suggest that structured, caregiver-focused approaches embedded in routine clinical pathways may strengthen dyadic chronic illness management. Full article

Background: The key parameters determining the bioavailability of an active pharmaceutical ingredient are its solubility/dissolution rate in physiological fluids and permeability across biological membranes. Highly accurate in vitro prediction of bioavailability is a key issue that typically arises during the development of new drug formulations and the improvement of existing ones. Objectives: The objective of the present work is to study the dissolution/release and permeation of olanzapine (OLZ) from two- and three-component solid dispersions (SDs) with sulfobutylether-β-cyclodextrin (SBE-β-CD) and several pharmaceutical adjuvants as solubilizing agents. Methods: Solid dispersions were prepared by mechanical grinding and characterized with X-ray Phase analysis (PXRD), Fourier Transform Infrared (FTIR) and Raman spectroscopy, Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM). Results: Raman spectroscopy was shown to be the best for revealing the interactions of OLZ with SBE-β-CD and γ-aminobutyric acid (GABA) in the three-component SD. The kinetic dependences of OLZ release and diffusion through the cellulose membrane were thoroughly described by quantitative parameters and classified according to the drug release mechanism. Significant improvement of release rate, OLZ concentration, and permeation with SDs compared to the pure OLZ was demonstrated. Conclusions: It was shown that the selected dispersions were stable when stored under normal conditions but underwent changes upon exposure to elevated temperature and humidity. The nature of these changes was determined by the properties of the components and their mutual interactions. Full article

Quercetin, one of the most abundant flavonoids in nature, has attracted the attention of many researchers due to its chemical and biological properties. A series of metal–quercetin complexes (Cu²⁺, Co²⁺, Zn²⁺, Sn²⁺, Al³⁺, Cd²⁺ and Mg²⁺) were synthesized and systematically characterized by Fourier transform infrared spectroscopy (FTIR), UV-visible spectroscopy (UV–Vis) and nuclear magnetic resonance (NMR). These analyses confirmed that the complexes predominantly form through coordination with the 4-carbonyl group and adjacent phenolic hydroxyls. This induces measurable shifts in the ν(C=O), ν(O–H), and π→π* transition bands relative to free quercetin. The antioxidant capacity of the complexes was evaluated using 2,2-Diphenyl-1-Picrylhydrazyl (DPPH^•) radical scavenging method, 2,2′-Azinobis(3-Ethylbenzothiazoline-6-Sulfonic Acid) (ABTS^•)⁺ radical activity, and Ferric Reducing Antioxidant Power (FRAP) assay. Several complexes exhibited higher radical scavenging efficiency than quercetin, with inhibition percentages exceeding 80% in the DPPH^• and ABTS^•+ assays. Others showed reduced activity due to the masking of redox-active hydroxyl groups during metal coordination. FRAP results corroborated these trends, indicating metal-dependent modulation of reducing power. Antimicrobial evaluation revealed that selected complexes were more active than free quercetin, particularly against Staphylococcus aureus and Candida spp., with minimum inhibitory concentrations (MICs) ranging from 75–250 μg mL⁻¹. Overall, metal complexation significantly alters the electronic structure and biological behavior of quercetin, highlighting the potential of metal–flavonoid complexes as multifunctional antioxidants and antimicrobials. Full article