Search Results (32,526)

Both organic matter and iron oxide (FeO) dynamics pose key roles in soil cadmium (Cd) bioavailability. However, the microbially driven transformation of soil organic matter and FeO and their linkages to Cd fractions remain unclear under reductive soil disinfestation (RSD) with different organic sources, which limits our mechanistic understanding of Cd immobilization by RSD. To address this gap, we conducted a 45 day microcosm experiment using a paddy soil contaminated with 22.8 mg/kg Cd. Six treatments were established: untreated control (CK), waterlogged (WF), and RSD-amended soils with 0.7% or 2.1% wheat straw (LWD, HWD) or soybean meal (LSD, HSD). We systematically assessed soil Cd fractionation, organic carbon and FeO concentrations, and bacterial community structure, aiming to clarify differences in Cd immobilization efficiency and the underlying mechanisms between wheat straw and soybean meal. For strongly extractable Cd, wheat straw RSD reduced the soil Cd concentrations from 6.02 mg/kg to 4.32 mg/kg (28.2%), whereas soybean meal RSD achieved a maximum reduction to 2.26 mg/kg (62.5%). Additionally, the soil mobility factor of Cd decreased from 44.6% (CK) to 39.2% (HWD) and 32.5% (HSD), while the distribution index increased from 58.5% (CK) to 62.2% (HWD) and 66.8% (HSD). Notably, the HWD treatment increased soil total organic carbon, humus, and humic acid concentrations by 34.8%, 24.6%, and 28.3%, respectively. Regarding amorphous FeO, their concentrations increased by 19.1% and 33.3% relative to CK. RSD treatments significantly altered soil C/N ratios (5.91–12.5). The higher C/N ratios associated with wheat straw stimulated r-strategist bacteria (e.g., Firmicutes, Bacteroidetes), which promoted carbohydrate degradation and fermentation, thereby enhancing the accumulation of humic substances. In contrast, the lower C/N ratios of soybean meal increased dissolved organic carbon and activated iron-reducing bacteria (FeRB; e.g., Anaeromyxobacter, Clostridium), driving iron reduction and amorphous iron oxide formation. PLS-PM analysis confirmed that wheat straw RSD immobilized Cd primarily through humification, whereas soybean meal RSD relied on FeRB-mediated FeO amorphization. These findings suggest that Cd immobilization in soil under RSD may be regulated by microbially mediated organic matter transformation and iron oxide dynamics, which was affected by organic materials of different C/N ratios. Full article

TIGIT and its ligand CD155 (PVR) are emerging immune checkpoints in colorectal cancer (CRC), but their associations with mutational subtypes and the tumor immune milieu remain unclear. We quantified TIGIT and CD155 proteins by ELISA in paired CRC tumors and matched surgical margins (n = 131) and evaluated associations with clinicopathological features, MSI status, and KRAS/NRAS/BRAF/PIK3CA/AKT1 mutations (n = 104). Both TIGIT and CD155 were significantly elevated in tumor tissue versus margins (p < 0.0001) and showed no association with TNM stage, clinical stage, grade, or tumor location. TIGIT levels were higher in MSI than MSS tumors and in BRAF-mutant compared to BRAF wild-type tumors, while CD155 expression showed no consistent MSI- or mutation-dependent differences. Cytokine profiling identified IFN-g as the only shared positive associate of TIGIT and CD155; CD155 additionally associated with TRAIL, IL-1Ra, M-CSF, and PDGF-bb. In external transcriptomic validation (TCGA-CRC), GSEA indicated enrichment of interferon/inflammatory programs in TIGIT-high tumors, while CD155-high tumors preferentially showed proliferation-related MYC/E2F/G2M signatures. Together, these findings support tumor-wide upregulation of the TIGIT/CD155 axis in CRC and suggest that TIGIT, more than CD155, tracks with MSI/BRAF-associated immune activation, providing a rationale for patient stratification in checkpoint-directed immunotherapy. Full article

The synthesis of carbon dots (CDs) from coal represents a promising strategy for advancing both the efficient, low-carbon utilization of coal resources and the cost-effective production of CDs. To enable the controlled, high-quality conversion of CDs from coal, a comprehensive understanding of the relationship between the coal chemical structure and the properties of CDs is crucial. This study prepared CDs from nine kinds of coal using a chemical oxidation method, and the correlations between properties of coal-based carbon dots and the original materials were revealed. The results show that the luminescence sites of coal-derived CDs are mostly distributed around 435 nm or 500 nm, where the former one relates to the confined sp² domains and the latter one is associated with the defect structure. Coal with a volatile content of about 20–30% in the nine samples was found to produce higher CD yields, with a maximum mass yield of 19.96%, accompanied by stronger fluorescence intensity. During chemical oxidation processes, the unsaturated double bonds (C=C, C=O) and aliphatic chains firstly break, and then aromatic clusters are formed by dehydrocyclization between carbon crystallites, followed by the introduction of a C–O group. The growth of the C–O group in the CDs contributes to a stronger fluorescence property. Furthermore, strong correlations were found between the carbon skeleton structure of raw coal and photoluminescence characteristics of corresponding CDs, as reflected by Raman parameters A_D1/A_G, I_D1/I_G, and FWHM_D. The findings offer significant insights into the precise modulation and control of coal-based carbon dot structures. Full article

Background/Objectives: Inter-individual variability in injury severity represents a major barrier to reproducibility in neonatal hypoxia–ischemia (HI) models. Objective early postoperative stratification of animals is therefore essential for standardized group allocation and reliable assessment of experimental outcomes. This study aimed to evaluate whether laser speckle contrast imaging (LSCI) can be used as a rapid, noninvasive tool for early post hoc stratification of ischemic brain damage severity in neonatal mice following HI. Methods: Neonatal CD-1 mice (postnatal day 9; n = 60) underwent hypoxia–ischemia using a modified Rice–Vannucci protocol. Cerebral perfusion was assessed by laser speckle contrast imaging at baseline, 3 h, and 7 days after HI. The difference in mean perfusion between ipsilateral and contralateral hemispheres at 3 h (Δ perfusion) was used to stratify animals into severity groups. Brain injury was quantified by 2,3,5-triphenyltetrazolium chloride (TTC) staining at 24 h and 7 days. Survival was monitored for 7 days and analyzed using Kaplan–Meier curves and the log-rank (Mantel–Cox) test. Results: LSCI-derived Δ perfusion at 3 h enabled the formation of distinct injury-severity groups (no visible damage, mild, moderate, and severe) with significant between-group differences (p < 0.0001). TTC-based lesion area increased stepwise across severity groups, and Δ perfusion correlated with lesion size when all animals were analyzed together (r = 0.688, p = 0.0011). No significant correlations were observed within individual severity groups, indicating that the overall association was driven primarily by between-group differences. Survival analysis revealed 75% mortality in the severe injury group (p < 0.0001). Conclusions: LSCI represents a robust and practical approach for early, objective, group-level stratification of neonatal mice by HI injury severity, thereby improving reproducibility and statistical validity in preclinical studies. However, its ability to predict outcomes within individual severity categories is limited, and repeated long-term measurements may pose technical challenges. Full article

Background/Objectives: Vedolizumab (VDZ), a monoclonal antibody targeting α4β7 integrin, is used in Crohn’s disease (CD) management, yet patients’ responses vary, underscoring the need for pharmacogenomic (PGx) markers. This study aimed to identify PGx pathways associated with suboptimal VDZ response using a rare-variant analytical framework. Methods: DNA from 63 CD patients treated with VDZ as first-line advanced therapy underwent whole-exome sequencing. Clinical response at week 14 classified patients as optimal responders (ORs) or suboptimal responders (SRs). Sequencing data were processed using GATK Best Practices, annotated with variant effect predictors, and filtered for rare damaging variants (damaging missense and high-confidence loss-of-function; minor allele frequency < 0.05). Variants were mapped to genes specific for SRs and ORs, and analyzed for pathway enrichment using the Reactome database. Rare-variant burden and composition differences were assessed with Fisher’s exact test and SKAT-O gene-set association analysis. Results: Suboptimal VDZ response was associated with pathways related to membrane transport (ABC-family proteins, ion channels), L1–ankyrin interactions, and bile acid recycling, while optimal response was associated with pathways involving MET signaling. SKAT-O identified lipid metabolism-related pathways as significantly different—SRs harbored variants in pro-inflammatory lipid signaling and immune cell trafficking genes (e.g., PIK3CG, CYP4F2, PLA2R1), whereas ORs carried variants in fatty acid oxidation and detoxification genes (e.g., ACADM, CYP1A1, ALDH3A2, DECR1, MMUT). Conclusions: This study underscores the potential of exome-based rare-variant analysis to stratify CD patients and guide precision medicine approaches. The identified genes and pathways are potential PGx markers for CD patients treated with VDZ. Full article

Sustainable groundwater management is critical in semi-arid coastal regions, where municipal landfills pose a severe threat to aquifer integrity and long-term water security. However, there is still a lack of seasonally resolved hydrogeochemical monitoring around newly established landfills, particularly in rapidly urbanizing Mediterranean settings. This study assesses the hydrogeochemical impact of the newly operational Tangier Landfill and Recovery Center on local groundwater resources to inform sustainable remediation strategies. A combined approach was applied to samples collected in dry and wet seasons, using Piper and Stiff diagrams to trace facies evolution together with a dual-index assessment based on the Canadian (CCME-WQI) and Weighted Arithmetic (WAWQI) Water Quality Indices. Results show that upgradient waters remain of Good–Excellent quality and are dominated by Ca–HCO₃ facies, whereas downgradient wells display extreme mineralization, with EC up to 15,480 µS/cm and Cl⁻ and SO₄²⁻ exceeding 1834 and 2114 mg/L, respectively. At hotspot sites P4 and P8, As reaches 0.065 mg/L and Cd 0.006 mg/L, far above the WHO drinking-water guidelines. While the CCME-WQI captures the general salinity-driven degradation pattern, the WAWQI pinpoints these acute toxicity zones as Very poor–Unsuitable. The study demonstrates that rainfall intensifies toxicity through a seasonal “Piston Effect” that mobilizes stored contaminants rather than diluting them, underscoring the need for seasonally adaptive monitoring to ensure the environmental sustainability of landfill-adjacent aquifers. Full article

Serum lactate dehydrogenase (LDH) is a recognized prognostic biomarker in human lymphomas, yet its clinical significance in canine lymphoma remains insufficiently characterized. This study aimed to quantify serum LDH levels in healthy dogs and dogs with high-grade multicentric lymphoma (ML) (predominantly B-cell) and to investigate correlations between LDH levels and established clinical and laboratory prognostic indicators. Twenty-seven dogs were prospectively enrolled: healthy controls (G1, n = 7) and dogs with high-grade ML (G2, n = 20). Immunophenotyping was performed by immunohistochemistry (CD3/CD79a). LDH concentrations were measured at diagnosis (T0) and after six weeks of CHOP-based induction chemotherapy (T1). Statistical analyses included Kruskal–Wallis, Wilcoxon signed-rank, Pearson’s correlation, and mixed-effects models. Dogs with high-grade ML exhibited significantly elevated LDH levels compared to controls (median 545.5 U/L, range: 288.2–2816 U/L vs. 143 U/L, range: 66–272; p < 0.001). Dogs with thrombocytopenia had higher baseline LDH (median 746 U/L, range: 612–921; p = 0.006) and greater reductions following chemotherapy (median −1011.7 U/L, range: −159 to −2064; p = 0.004). LDH levels declined significantly after treatment (overall median reduction 50.7%; post-chemotherapy range: 60.4–752 U/L; n = 15; p = 0.013), with normalization achieved in 77.8% of dogs with complete response versus 16.7% with partial or progressive disease (p = 0.02). We confirmed that serum LDH is significantly elevated in dogs with high-grade ML and declines following effective chemotherapy, supporting its utility as a dynamic biomarker of tumor burden and treatment response. Thrombocytopenic dogs may represent a biologically distinct subset warranting further investigation. Full article

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of long-term cardiovascular complications, including elevated blood pressure, endothelial dysfunction, and arterial stiffness. Endothelial progenitor cells (EPCs), particularly endothelial colony-forming cells (ECFCs), play a critical role in maintaining vascular homeostasis. Previously, Simoncini et al. observed that in a rat model of IUGR, six-month-old males exhibited elevated systolic blood pressure (SBP) and microvascular rarefaction compared with control (CTRL) rats. These vascular alterations were accompanied by reduced numbers and impaired function of bone marrow-derived ECFCs, which were associated with oxidative stress and stress-induced premature senescence (SIPS). In contrast, IUGR females of the same age and from the same litter did not exhibit higher SBP or microvascular rarefaction, raising the question of whether ECFC dysfunction in IUGR female rats can be present without vascular alterations. So, we investigated ECFCs isolated from six-month-old female IUGR offspring (maternal 9% casein diet) and CTRL females (23% casein diet). To complete the vascular assessment, we performed in vivo and in vitro investigations. No alteration in pulse wave velocity (measured by echo-Doppler) was observed; however, IUGR females showed decreased aortic collagen and increased elastin content compared with CTRL. Regarding ECFCs, those from IUGR females maintained their endothelial identity (CD31⁺/CD146⁺ ratio among viable CD45⁻ cells) but exhibited slight alterations in progenitor marker expression (CD34) compared with those of CTRL females. Functionally, IUGR-ECFCs displayed a delayed proliferation phase between 6 and 24 h, while their ability to form capillary-like structures remained unchanged, however their capacity to form capillary-like structures was preserved. Regarding the nitric oxide (NO) pathway, a biologically relevant trend toward reduced NO levels and decreased endothelial nitric oxide synthase expression was observed, whereas oxidative stress and SIPS markers remained unchanged. Overall, these findings indicate that ECFCs from six-month-old female IUGR rats exhibit only minor functional alterations, which may contribute to vascular protection against increase SBP, microvascular rarefaction, and arterial stiffness. Full article

Objective: To better define potential executive function difficulties in individuals living with HIV but not clinically identified as having HAND, with and without mild to moderate cocaine dependence (CD), our cross-sectional study examined executive function performance on the Stroop Color-Word Test (Stroop) and the Trail Making Test (TMT) in four groups stratified by HIV and CD status. Method: We recruited 101 participants (26 HIV+/CD+; 18 HIV+/CD−; 30 HIV−/CD+; 27 HIV−/CD−). We utilized a 2 (HIV: yes/no) × 2 (Cocaine: yes/no) MANCOVA while controlling for age and premorbid intelligence on the Stroop trials (i.e., color-naming, word-reading, interference), and TMT-A and TMT-B z-scores, number of errors, and the B/A ratio. Results: HIV was associated with significantly slower performance on the Stroop Interference (p = 0.012, η² = 0.064). CD showed a trend towards slower performance on interference trials (p = 0.061, η² = 0.037) and was associated with significantly more errors on the Stroop Word-Reading (p = 0.028, η² = 0.050) and Interference trials (p = 0.046, η² = 0.041), suggestive of difficulties with inhibitory control and written language processing. There were no significant HIV × Cocaine interactions. Conclusions: Our results suggest HIV without clinically identified cognitive impairment and CD are associated with distinct and potentially overlapping executive functioning deficits, particularly for measures of inhibitory control. Notably, CD showed trend-level slowing on Stroop Interference performance, suggesting partial overlap with HIV effects. Clarifying the specific cognitive processes impacted by HIV and CD can help guide tailored interventions to improve functional outcomes in these populations. Full article

The accumulation of heavy metals in fish tissues is widely recognized as an indicator of aquatic environmental pollution, and the analysis of their content provides a basis for assessing ecological risk and the safety of aquatic food. The European eel (Anguilla anguilla) is a species frequently used as a bioindicator in environmental studies due to its wide geographic distribution, long life cycle, and high capacity for bioaccumulation of heavy metals in various tissues. The aim of this study was to assess the variation in the accumulation of heavy metals, i.e., mercury (Hg), lead (Pb), arsenic (As), and cadmium (Cd), in the tissues (muscle, liver, gonads, and gills) of European eels caught in two locations in Polish inland waters. The obtained results showed significant differences both in the concentration levels of individual elements and in their co-occurrence in the examined tissues. The statistical methods used, including correlation analysis, heat maps, and principal component analysis (PCA), allowed for a comprehensive assessment of the relationships between metals and the identification of factors differentiating the studied populations. The obtained results clearly indicate that fish residing in similar environments for long periods exhibit significant differences in heavy metal content in various fish tissues. Fish obtained from environments with potentially higher levels of heavy metal inputs, such as the Oder River EMU compared with the Vistula River EMU, showed higher levels of heavy metal accumulation in tissues. This study also found that the concentration of heavy metals tested did not exceed the safe standards for human fish consumption. Full article

Accumulating evidence suggests that exposure to pollution from environmental cadmium (Cd) contributes to diabetic kidney disease as indicated by albuminuria and a progressive decrease in the estimated glomerular filtration rate (eGFR). This study examined the effects of Cd exposure on eGFR and the excretion rates of albumin (E_alb) and β₂-microglobulin (E_β2M) in 65 diabetics and 72 controls. Excretion of Cd (E_Cd) was a measure of exposure, while excretion of N-acetylglucosaminidase (E_NAG) reflected the extent of kidney tubular cell injury. In participants with an elevated excretion of E_β2M, the prevalence odds ratios (POR) for a reduced eGFR rose 6.4-fold, whereas the POR for albuminuria rose 4.3-fold, 4.1-fold, and 2.8-fold in those with a reduced eGFR, diabetes, and hypertension, respectively. Using covariance analysis, which adjusted for the interactions, 43% of the variation in E_alb among diabetics could be explained by female gender (η² = 0.176), E_NAG (η² = 0.162), hypertension (η² = 0.146), smoking (η² = 0.107), and body mass index (η² = 0.097), while the direct contribution of E_Cd to E_alb variability was minimal (η² = 0.005). Results from a mediating-effect analysis imply that Cd could contribute to albuminuria and a falling eGFR through inducing tubular cell injury, leading to reduced reabsorption of albumin and β₂M. Full article

Cannabinoids can bind to several cannabinoid receptors and modulate cellular signaling and gene expression relevant to inflammation and lipid homeostasis. Likewise, several vitamin E analogs can modulate inflammatory signaling and foam cell formation in macrophages by antioxidant and non-antioxidant mechanisms. We analyzed the regulatory effects on the expression of genes involved in cellular lipid homeostasis (e.g., CD36/FAT cluster of differentiation/fatty acid transporter and scavenger receptor SR-B1) and inflammation (e.g., inflammatory cytokines, TNFα, IL1β) by cannabinoids (cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC)) in human THP-1 macrophages with/without co-treatment with natural alpha-tocopherol (RRR-αT), natural RRR-αTA (αTAn), and synthetic racemic all-rac-αTA (αTAr). In general, αTAr inhibited both lipid accumulation and the inflammatory response (TNFα, IL6, IL1β) more efficiently compared to αTAn. Our results suggest that induction of CD36/FAT mRNA expression after treatment with THC can be prevented, albeit incompletely, by αTA (either αTAn or αTAr) or CBD. A similar response pattern was observed with genes involved in lipid efflux (ABCA1, less with SR-B1), suggesting an imbalance between uptake, metabolism, and efflux of lipids/αTA, increasing macrophage foam cell formation. THC increased reactive oxygen species (ROS), and co-treatment with αTAn or αTAr only partially prevented this. To study the mechanisms by which inflammatory and lipid-related genes are modulated, HEK293 cells overexpressing cannabinoid receptors (CB1 or TRPV-1) were transfected with luciferase reporter plasmids containing the human CD36 promoter or response elements for transcription factors involved in its regulation (e.g., LXR and NFκB). In cells overexpressing CB1, we observed activation of NFκB by THC that was inhibited by αTAr. Full article

Ulcerative colitis (UC) is a chronic progressive inflammatory bowel disease, with evolutive potential for extension to the entire colon, development of complications and need for colectomy. Therapeutic goals in UC have moved from symptom control to more stringent outcomes such as endoscopic and histologic remission, which have been observed to correlate with improved long-term outcomes. Disease clearance, a composite endpoint simultaneously including clinical remission, endoscopic and histologic healing, has been recently proposed as the ultimate target. A treat-to-target approach, as endorsed by the STRIDE II consensus, with a tight monitoring and treatment escalation when predefined endpoints are not reached, is proposed as a strategy to achieve complete disease control. However, unlike Crohn’s disease (CD), the evidence supporting this approach for the management of UC is limited and its implementation in routine clinical practice is not widely diffused. Recent real-life data show that almost half of UC patients are not adequately controlled with current therapies according to STRIDE II criteria, due to steroid overuse, persistent signs of inflammation, active extra-intestinal manifestations and impaired quality of life. This perspective paper explores current evidence and future directions on treat-to-target strategies in UC for clinical research and practice. Full article

Regulatory T cells (Tregs), particularly their phenotypically distinct subpopulations, are critical for the establishment of maternal immune tolerance during embryo implantation. Despite advances in assisted reproductive technologies, implantation failure remains a frequent and often unexplained clinical challenge. Variations in Treg frequency and phenotype have been proposed to influence implantation success, particularly under differing hormonal conditions. This study aimed to investigate peripheral blood Treg levels and their subpopulations on the day of blastocyst transfer in both stimulated in vitro fertilization (IVF/ICSI) cycles involving controlled ovarian hyperstimulation (COH) and true natural cycles with frozen embryo transfer (FET), and to examine their associations with systemic hormone levels and anti-Müllerian hormone (AMH). A prospective observational study was conducted including women undergoing IVF/ICSI with fresh embryo transfer (ET) and women undergoing natural cycle FET. Peripheral blood samples were collected on the day of ET and analyzed using 13-colour flow cytometry, enabling detailed subdivision of Tregs into multiple subpopulations based on the expression of differentiation and chemokine markers, including CXCR5. In addition, because common $\gamma$-chain cytokines may influence pregnancy success by modulating the balance between suppressive Treg and non-Treg subsets, intracellular STAT5 signaling was assessed using phospho-specific flow cytometry. Serum estradiol, progesterone, FSH, LH, and AMH levels were measured in parallel. Significant differences were observed in Treg subpopulation distributions between women who conceived and those who did not. Higher frequencies of naïve CXCR5⁻ Tregs were associated with clinical pregnancy, independent of age, and correlated with serum progesterone levels. Moreover, both naïve Treg frequency and enhanced IL-7-dependent STAT5 signaling in naïve Tregs from women undergoing COH were associated with AMH levels, suggesting a link between ovarian reserve and Treg homeostasis mediated by signal transducer and activator of transcription 5 (STAT5) signaling. In conclusion, Treg subpopulations, particularly CXCR5⁻ naïve Tregs, appear to play a central role in implantation success following ET. Their distribution differs between stimulated and natural cycles and is influenced by systemic progesterone levels and STAT5 signaling. These findings suggest that peripheral Treg profiling may represent a potential biomarker of implantation competence and could inform personalized approaches in assisted reproduction. Full article

Chimeric antigen receptor (CAR) T cell therapy has demonstrated clinical success in hematologic malignancies but has limited efficacy in solid tumors due to tumor microenvironment (TME) barriers that impede CAR T cell recognition, infiltration, and sustained function. Traditional 2D assays inadequately recapitulate these constraints, necessitating improved in vitro models. This study validated a 3D tumor spheroid platform using an agarose microwell system to generate uniform B7-H3-positive spheroids from multiple solid tumor cell lines, enabling the evaluation of CAR T cell activity. TME-relevant immune modulation under 3D conditions was analyzed by flow cytometry for B7-H3, MHC I/II, and antigen processing machinery (APM), followed by co-culture with B7-H3 CAR T cells to assess cytotoxicity, spheroid integrity, tumor viability, and CAR T cell activation, exhaustion, and cytokine production. Two human cancer-cell-line-derived spheroids, DU 145 (prostate cancer) and SUM159 (breast cancer), retained B7-H3 expression, while MC38 (mouse colon cancer)-derived spheroids served as a B7-H3 negative control. Under 3D culture conditions, DU 145 and SUM159 spheroids acquire TME-like immune evasion characteristics and specifically downregulated MHC-I and APM (TAP1, TAP2, LMP7) with concurrent upregulation of MHC-II and calreticulin. Co-culture showed effective spheroid infiltration, cytotoxicity, and structural disruption, with infiltrating CAR T cells displaying higher CD4⁺ fraction, activation, exhaustion, effector/terminal differentiation, and IFN-γ/TNF-α production. This 3D platform recapitulates critical TME constraints and provides a cost-effective, feasible preclinical tool to assess CAR T therapies beyond conventional 2D assays. Full article