Search Results (30,403)

Autologous therapies are currently being studied to determine if they can modulate the course of knee osteoarthritis symptoms and/or disease progression. One potential therapeutic target is the polarization of pro-inflammatory M1 macrophages to pro-healing M2 macrophages. The autologous therapy, Autologous Protein Solution (APS), was incubated with donor-matched human peripheral-derived macrophages for 10 days. M1 pro-inflammatory macrophages were determined by the percentage of CD80+ and M2 pro-healing macrophages were determined by CD68+ and CD163+ by epifluorescent microscopy. To determine clinical effectiveness, an APS-specific minimal clinically important improvement (MCII) using an anchor-based method was calculated in a randomized controlled trial of APS (n = 46) and then applied to a real-world registry study (n = 78) to determine the percentage of pain responders. Compared to control media, APS statistically increased the percentage of M2 macrophages and decreased the percentage of M1 macrophages, while platelet-poor plasma had no effect on polarization. In the randomized controlled trial (RCT), the MCII at the 12-month follow-up visit was calculated as 2.0 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale and 7.5 points on the WOMAC function scale. Applying this MCII to the real-world registry data, 62.5% of patients met the MCII with an average of 4.7 ± 2.5 points of improvement in pain. Autologous therapies can influence macrophage polarization and have demonstrated clinical effectiveness in a real-world patient setting. Full article

Fyn is widely involved in diverse cellular physiological processes, including cell growth and survival, and has been implicated in the regulation of energy metabolism and the pathogenesis of diabetes mellitus through multiple pathways. Fyn plays a role in increasing fat accumulation and promoting insulin resistance, and it also contributes to the development of diabetic complications such as diabetic kidney disease and diabetic retinopathy. The primary mechanism by which Fyn modulates lipid metabolism is that it inhibits AMP-activated protein kinase (AMPK). Additionally, it affects energy homeostasis through regulating specific signal pathways affecting lipid metabolism including pathways related to CD36, through enhancement of adipocyte differentiation, and through modulating insulin signal transduction. Inflammatory stress is one of the fundamental mechanisms in diabetes mellitus and its complications. Fyn also plays a role in inflammatory stress-related signaling cascades such as the Akt/GSK-3β/Fyn/Nrf2 pathway, exacerbating inflammation in diabetes mellitus. Therefore, Fyn emerges as a promising therapeutic target for regulating glucolipid metabolism and alleviating type 2 diabetes mellitus. This review synthesizes research on the role of Fyn in the regulation of energy metabolism and the development of diabetes mellitus, while exploring its specific regulatory mechanisms. Full article

Reactions of the angular 4,4′-oxybis[N-(pyridin-3-ylmethyl)benzamide] (L) with dicarboxylic acids and transition metal salts afforded non-entangled {[Cd(L)(1,3-BDC)(H₂O)]∙2H₂O}_n (1,3-BDC = 1,3-benzenedicarboxylic acid), 1; {[Cd(L)(1,4-HBDC)(1,4-BDC)_0.5]∙2H₂O}_n (1,4-BDC = 1,4-benzenedicarboxylic acid), 2; {[Cu₂(L)₂(1,3-BDC)₂]∙1.5H₂O}_n, 3; {[Ni(L)(1,3-BDC)(H₂O)]∙2H₂O}_n, 4; {[Zn(L)(1,3-BDC)]∙4H₂O}_n, 5; {[Zn(L)(1,4-BDC)]∙2H₂O}_n, 6; and [Cd₃(L)₂(1,4-BDC)₃]_n, 7, which have been structurally characterized by using single-crystal X-ray diffraction. Complexes 1–5 and 7 are 2D layers, giving (6⁴·8·10)(6)-2,4L3, (4²·8²·10²)(4²·8⁴)₂(4)₂, (4·5·6)(4·5⁵·6³·7)-3,5L66, (6⁴·8·10)(6)-2,4L3, interdigitated (8⁴·12²)(8)₂-2,4L2 and (3⁶·4⁶·5³)-hxl topologies, respectively, and 6 is a 1D chain with the (4³·6²·8)(4)-2,4C3 topology. The factors that govern the structures of 1–7 are discussed and the thermal properties of 1–7 and the luminescent properties of complexes 1, 2, 5 and 6 are investigated. The stabilities of complexes 1 and 5 toward the detection of Fe³⁺ ions are also evaluated. Full article

Background: Workplace mobbing is a widespread phenomenon with serious psychological and emotional consequences on employees’ emotional well-being. Psychological resilience has been identified as a potential protective factor against such adverse outcomes. Aim: This study investigates the relationship between workplace mobbing and emotional well-being, as expressed through positive and negative affect, and examines the mediating role of psychological resilience in this association. Methods: Ninety nurses participated in this cross-sectional study. Data were collected using the Connor–Davidson Resilience Scale (CD-RISC), the Workplace Psychologically Violent Behaviors (WPVB) scale, and the Positive and Negative Affect Schedule (PANAS). Statistical analyses included correlation, multiple regression, and mediation using bootstrapped confidence intervals. Results: Resilience was strongly associated with positive affect (r = 0.74, p < 0.001) and inversely with negative affect (r = −0.46, p < 0.001). Mobbing was significantly related to increased negative affect (β = 0.12, p < 0.001) but not to positive affect. Resilience emerged as the strongest predictor of emotional outcomes and partially mediated the relationship between “Attack on professional role” and negative affect. Conclusions: Psychological resilience plays a key protective role in moderating the emotional impact of workplace mobbing. Enhancing resilience in healthcare professionals may mitigate the negative emotional effects of mobbing, although it does not fully buffer against all its consequences. Full article

One hundred presumptive Pseudomonas isolates, recovered from 15 sites impacted by anthropogenic activity in the Foggia district (Italy), were screened for key adaptive and functional traits important for environmental applications. The isolates were phenotypically characterized for their ability to grow under combined pH (5.0–8.0) and temperature (15–37 °C) conditions, to produce proteolytic enzymes, pigments, and exopolysaccharides, and to tolerate SDS. Moreover, the resistance to six environmentally relevant heavy metals (Cd, Co, Cu, Ni, Zn, As) was qualitatively assessed. The results highlighted wide inter-strain variability, with distinct clusters of isolates showing unique combinations of stress tolerance, enzymatic potential, and resistance profile. PERMANOVA analysis revealed significant effects of both the isolation site and the metal type, as well as their interaction, on the observed resistance patterns. A subset of isolates showed co-tolerance to elevated temperatures and heavy metals. These findings offer an initial yet insightful overview of the adaptive diversity of soil-derived Pseudomonas, laying the groundwork for the rational selection of strains for bioaugmentation in contaminated soils. Full article

Glioma is a type of neoplasia that spontaneously arises from the glial cells of the brain in humans and dogs, and its prognosis is grave. Current treatment options for glioma include surgery, radiation therapy, chemotherapy, or symptomatic treatment. Evidence has shown that cannabidiol (CBD) may have anticancer, anti-angiogenic, and anti-inflammatory properties in both in vitro and in vivo studies. In this in vivo murine experiment, the canine glioma cell line J3TBG was injected into the frontoparietal cortex of immunodeficient mice using xenogeneic tissue transplantation. A total of 20 mice were randomly assigned to one of four treatment groups—Control group (C), CBD group (CBD), Radiation Therapy group (RT), and CBD plus Radiation Therapy group (CBD + RT). After transplantation of J3TBG, a single fraction of 5.5 Gy RT was administered to the RT and CBD + RT groups, and CBD was administered daily to the CBD and CBD + RT groups. Necropsies were performed to collect blood and brain tissue. Although there was not a statistically significant difference, the survival time among mice were longer in the CBD + RT group than the RT group. These results indicate that CBD may be used as an adjunctive therapy to enhance RT treatment. Larger cohort studies are required to substantiate the hypothesis. Full article

Degradable fluorescent sensors present a promising portable approach for heavy metal ion detection, aiming to prevent secondary environmental pollution. Additionally, the excessive intake of ferric ions (Fe³⁺), an essential trace element for human health, poses critical health risks that urgently require effective monitoring. In this study, we developed a thermally degradable fluorescent hydrogel sensor (Eu-CDs@DPPG) based on europium-doped carbon dots (Eu-CDs). The Eu-CDs, synthesized via a hydrothermal method, exhibited selective fluorescence quenching by Fe³⁺ through the inner filter effect (IFE). Embedding Eu-CDs into the hydrogel significantly enhanced their stability and dispersibility in aqueous environments, effectively resolving issues related to aggregation and matrix interference in traditional sensing methods. The developed sensor demonstrated a broad linear detection range (0–2.5 µM), an extremely low detection limit (1.25 nM), and rapid response (<40 s). Furthermore, a smartphone-assisted LAB color analysis allowed portable, visual quantification of Fe³⁺ with a practical LOD of 6.588 nM. Importantly, the hydrogel was thermally degradable at 80 °C, thus minimizing environmental impact. The sensor’s practical applicability was validated by accurately detecting Fe³⁺ in spinach and human urine samples, achieving recoveries of 98.7–108.0% with low relative standard deviations. This work provides an efficient, portable, and sustainable sensing platform that overcomes the limitations inherent in conventional analytical methods. Full article

Background: Moral harassment (mobbing) in healthcare, particularly among nurses, remains a persistent issue with detrimental effects on mental health, resilience, and quality of life. Aim: We examine the relationship between the resilience of nurses working in Emergency Departments (EDs) and how these factors influence experiences of workplace mobbing. Methods: This cross-sectional study included 90 nurses from four public hospitals in Greece’s 5th Health District. Data were collected between October 2023 and March 2024 using the WHOQOL-BREF, Workplace Psychologically Violent Behaviors (WPVB) scale and the Connor–Davidson Resilience Scale (CD-RISC). The sample consisted primarily of full-time nurses (84.3% female; mean age = 43.1 years), with 21.1% reporting chronic conditions. Most participants were married (80.0%) and had children (74.4%), typically two (56.1%). Statistical analyses—conducted using SPSS version 27.0—included descriptive statistics, Pearson and Spearman correlations, multiple linear regression, and mediation analysis, with significance set at p < 0.05. Results: Resilience was moderate (mean = 66.38%; Cronbach’s α = 0.93) and positively correlated with all WHOQOL-BREF domains—physical, psychological, social, and environmental (r = 0.30–0.40)—but not with the overall WHOQOL-BREF. The mean overall WHOQOL-BREF score was 68.4%, with the lowest scores observed in the environmental domain (mean = 53.76%). Workplace mobbing levels were low to moderate (mean WPVB score = 17.87), with subscale reliabilities ranging from α = 0.78 to 0.95. Mobbing was negatively associated with social relationships and the environmental WHOQOL-BREF (ρ = –0.23 to –0.33). Regression analysis showed that cohabitation and higher resilience significantly predicted better WHOQOL-BREF outcomes, whereas mobbing was not a significant predictor. Mediation analysis (bootstrap N = 5000) indicated no significant indirect effect of resilience in the relationship between mobbing and WHOQOL-BREF. Conclusions: Resilience was identified as a key protective factor for nurses’ quality of life in emergency care settings. Although workplace mobbing was present at low-to-moderate levels, it was negatively associated with specific WHOQOL-BREF domains. Enhancing mental resilience among nurses may serve as a valuable strategy to mitigate the psychological effects of moral harassment in healthcare environments. Full article

Background Plasma membrane proteins (PMPs) play key roles in cell signalling, adhesion, and trafficking, and are attractive therapeutic targets in cancer due to their surface accessibility. However, their typically low abundance limits detection by conventional proteomic approaches. Methods: To improve PMP detection, we employed a surface proteomics workflow combining cell surface biotinylation and affinity purification prior to LC-MS/MS analysis in cervical (SiHa) and bladder (UMUC3) cancer cell lines cultured under normoxic (21% O₂) or hypoxic (0.1% O₂) conditions. Results: In SiHa cells, 43 hypoxia-upregulated proteins were identified exclusively in the biotin-enriched fraction, including ITGB2, ITGA7, AXL, MET, JAG2, and CAV1/CAV2. In UMUC3 cells, 32 unique upregulated PMPs were detected, including CD55, ADGRB1, SLC9A1, NECTIN3, and ACTG1. These proteins were not observed in corresponding whole-cell lysates and are associated with extracellular matrix remodelling, immune modulation, and ion transport. Biotinylation enhanced the detection of membrane-associated pathways such as ECM organisation, integrin signalling, and PI3K–Akt activation. Protein–protein interaction analysis revealed links between membrane receptors and intracellular stress regulators, including mitochondrial proteins. Conclusions: These findings demonstrate that surface biotinylation improves the sensitivity and selectivity of plasma membrane proteomics under hypoxia, revealing hypoxia-responsive proteins and pathways not captured by standard whole-cell analysis. Full article

HgCdSe has recently been proposed as a potential alternative material to HgCdTe for fabricating high-performance infrared detectors. This work presents a study on the growth of high-crystalline-quality HgCdSe materials on GaSb (211)B substrates via molecular beam epitaxy and demonstration of the first prototype HgCdSe-based mid-wave infrared detectors. By optimizing the MBE growth parameters, and especially the thermal cleaning process of the GaSb substrate surface prior to epitaxial growth, high-quality HgCdSe material was achieved with a record XRD full width at half maximum of ~65 arcsec. At a temperature of 77 K, the mid-wave infrared HgCdSe n-type material demonstrated a minority carrier lifetime of ~1.19 µs, background electron concentration of ~2.2 × 10¹⁷ cm⁻³, and electron mobility of ~1.6 × 10⁴ cm²/Vs. The fabricated mid-wave infrared HgCdSe photoconductor presented a cut-off wavelength of 4.2 µm, a peak responsivity of ~40 V/W, and a peak detectivity of ~1.2 × 10⁹ cmHz^1/2/W at 77 K. Due to the relatively high background electron concentration, the detector performance is lower than that of state-of-the-art low-doped HgCdTe counterparts. However, these preliminary results indicate the great potential of HgCdSe materials for achieving next-generation IR detectors on large-area substrates with features of lower cost and larger array format size. Full article

Wild edible mushrooms are increasingly recognised for their nutritional and therapeutic potential, owing to their richness in bioactive compounds and antioxidant properties. This study assessed the chemical composition, antioxidant capacity, and bioaccumulation of heavy metals (Cd, Pb, Ni) in Boletus edulis, Imleria badia, and Leccinum scabrum collected from two forested regions of north-western Poland differing in anthropogenic influence and soil characteristics. The analysis encompassed structural polysaccharides (β- and α-glucans, chitin), carotenoids, L-ascorbic acid, phenolic and organic acids. B. edulis exhibited the highest β-glucan and lycopene contents, but also the greatest cadmium accumulation. I. badia was distinguished by elevated ascorbic and citric acid levels and the strongest DPPH radical scavenging activity, while L. scabrum showed the highest ABTS and FRAP antioxidant capacities and accumulated quinic acid and catechin. Principal component analysis indicated strong correlations between antioxidant activity and phenolic acids, while cadmium levels were inversely associated with antioxidant potential and positively correlated with chitin. Although all metal concentrations remained within EU food safety limits, B. edulis showed consistent cadmium bioaccumulation. From a practical perspective, the results highlight the importance of species selection and sourcing location when considering wild mushrooms for consumption or processing, particularly in the context of nutritional value and contaminant load. Importantly, regular or excessive consumption of B. edulis may result in exceeding the tolerable weekly intake (TWI) levels for cadmium and nickel, which warrants particular attention from a food safety perspective. These findings underscore the influence of species-specific traits and environmental conditions on mushroom biochemical profiles and support their potential as functional foods, provided that metal contents are adequately monitored. Full article

South Dongting Lake is an essential aquatic ecosystem that receives substantial water inflows from the Xiangjiang and Zishui Rivers. However, it is significantly impacted by human activities, including mining, smelting, and farming. These activities have led to serious contamination of the lake’s sediments with heavy metals (HMs). This study investigated the distribution, mobility, and influencing factors of HMs at the sediment–water interface. To this end, sediment samples were analyzed from three key regions (Xiangjiang River estuary, Zishui River estuary, and northeastern South Dongting Lake) using traditional sampling methods and Diffusive Gradients in Thin Films (DGT) technology. Analysis of fifteen HMs (Pb, Bi, Ni, As, Se, Cd, Sb, Mn, Zn, V, Cr, Cu, Tl, Co, and Fe) revealed significant spatial heterogeneity. The results showed that Cr, Cu, Pb, Bi, Ni, As, Se, Cd, Sb, Mn, Zn, and Fe exhibited high variability (CV > 0.20), whereas V, Tl, and Co demonstrated stable concentrations (CV < 0.20). Concentrations were found to exceed background values of the upper continental crust of eastern China (UCC), Yangtze River sediments (YZ), and Dongting Lake sediments (DT), particularly at the Xiangjiang estuary (XE) and in the northeastern regions. Speciation analysis revealed that V, Cr, Cu, Ni, and As were predominantly found in the residual fraction (F4), while Pb and Co were concentrated in the oxidizable fraction (F3), Mn and Zn appeared primarily in the exchangeable fractions (F1 and F2), and Cd was notably dominant in the exchangeable fraction (F1), suggesting a high potential for mobility. Additionally, DGT results confirmed a significant potential for the release of Pb, Zn, and Cd. Contamination assessment using the Pollution Load Index (PLI) and Geoaccumulation Index (Igeo) identified Pb, Bi, Ni, As, Se, Cd, and Sb as major pollutants. Among these, Bi and Cd were found to pose the highest risks. Furthermore, the Risk Assessment Code (RAC) and the Potential Ecological Risk Index (PERI) highlighted Cd as the primary ecological risk contributor, especially in the XE. The study identified sediment grain size, pH, electrical conductivity, and nutrient levels as the primary influencing factors. The PMF modeling revealed HM sources as mixed smelting/natural inputs, agricultural activities, natural weathering, and mining/smelting operations, suggesting that remediation should prioritize Cd control in the XE with emphasis on external inputs. Full article

Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article

Although PD-1/PD-L1 inhibitors have transformed cancer immunotherapy, a substantial proportion of patients derive no clinical benefit due to resistance driven by the tumour microenvironment (TME). Transforming growth factor-β (TGF-β) is a key immunosuppressive cytokine implicated in this resistance. Several bifunctional antibodies that co-target PD-1 and TGF-β signalling have entered clinical trials and shown encouraging efficacy, but the mechanistic basis of their synergy is not fully understood. Here, we engineered 015s, a bifunctional fusion antibody that simultaneously targets murine PD-1 and TGF-β and evaluated its antitumour efficacy and mechanistic impact in pre-clinical models. Antibody 015s exhibited high affinity, dual target binding, and the effective inhibition of PD-1 and TGF-β signalling. In vivo, 015s significantly suppressed tumour growth compared with anti-mPD-1 or TGF-β receptor II (TGF-βRII) monotherapy. When combined with the CD24-targeted ADC, 015s produced even greater antitumour activity and achieved complete tumour regression. Mechanistic studies demonstrated that 015s significantly reduced tumour cell migration and invasion, reversed epithelial–mesenchymal transition (EMT), decreased microvascular density, and attenuated collagen deposition within the TME. Antibody 015s also decreased bioactive TGF-β1 and increased intratumoural IFN-γ, creating a more immunostimulatory milieu. These findings support further development of PD-1/TGF-β bifunctional antibodies for cancers with high TGF-β activity or limited response to immune checkpoint blockade. Full article

Gastrointestinal (GI) cancers represent a significant global health burden, with high morbidity and mortality often linked to late-stage detection and metastatic disease. The progression of these malignancies is critically driven by angiogenesis, the formation of new blood vessels, and the surrounding dynamic tumor microenvironment (TME), a complex ecosystem comprising various cell types and non-cellular components. This comprehensive review, based on a systematic search of the PubMed database, synthesizes the existing literature to define the intertwined roles of angiogenesis and the TME in GI tumorigenesis. The TME’s influence creates conditions favorable for tumor growth, invasion, and metastasis, but sometimes induces resistance to current therapies. Available therapeutic strategies for inhibiting angiogenesis involve antibodies and oral tyrosine kinase inhibitors, while immune modulation within the tumor microenvironment is mainly achieved through checkpoint inhibitor antibodies and chemotherapy. Creative emerging strategies encompassing cellular therapies, bispecific antibodies, and new targets such as CD40, DLL4, and Ang2, amongst others, are focused on inhibiting proangiogenic pathways more profoundly, reversing resistance to prior drugs, and modulating the TME to enhance therapeutic efficacy. A deeper understanding of the complex interactions between components of the TME is crucial for addressing the unmet need for novel and effective therapeutic interventions against aggressive GI cancers. Full article