Search Results (302)

Pharmaceuticals are increasingly being detected in coastal ecosystems globally, but contamination and bioaccumulation levels are understudied in temporarily closed estuaries. In these systems, limited freshwater inputs and periodic closure may predispose them to pharmaceutical accumulation. We quantified in situ water column pharmaceutical levels at five sites in a temporarily closed model urban estuary (Zandvlei Estuary) in Cape Town, South Africa, that has been heavily anthropogenically modified. The results indicate an almost 100-fold greater concentration of pharmaceuticals in the estuary relative to False Bay, into which the estuary discharges, with acetaminophen (max: 2.531 µg/L) and sulfamethoxazole (max: 0.138 µg/L) being the primary pollutants. Acetaminophen was potentially bioaccumulative, while nevirapine, carbamazepine and sulfamethoxazole were bioaccumulated (BAF > 5000 L/kg) by sandprawns (Kraussillichirus kraussi), which are key coastal endobenthic ecosystem engineers in southern Africa. The assimilative capacity of temporarily closed estuarine environments may be adversely impacted by wastewater discharges that contain diverse pharmaceuticals, based upon the high bioaccumulation detected in key benthic engineers. Full article

Urban parks are an integral component of cities; however, they are susceptible to heavy metal contamination from anthropogenic sources. Here, we investigated the moss Pleurozium schreberi and tree leaves as bioindicators for monitoring heavy metal contamination in urban parks. We determined heavy metal concentrations in P. schreberi, leaf tissues of selected tree species, and soil samples collected from various locations within a designated urban parks. The order of heavy metal accumulation was Zn > Pb > Cr > Cu > Ni > Cd > Hg in soil and Zn > Cu > Pb > Cr > Ni > Cd > Hg in P. schreberi. The order was Zn > Cu > Cr > Ni > Pb > Cd > Hg in linden and sycamore leaves, while birch leaves displayed a similar order but with slightly more Ni than Cr. The heavy metal concentration in the tested soils correlated positively with finer textures (clay and silt) and negatively with sand. The highest metal accumulation index (MAI) was noted in birch and P. schreberi, corresponding to the highest total heavy metal accumulation. The bioconcentration factor (BAF) was also higher in P. schreberi, indicating a greater ability to accumulate heavy metals than tree leaves, except silver birch for Zn in one of the parks. Silver birch displayed the highest phytoremediation capacity among the analysed tree species, highlighting its potential as a suitable bioindicator in heavy metal-laden urban parks. Our findings revealed significant variation in heavy metal accumulation, highlighting the potential of these bioindicators to map contamination patterns. Full article

The application of animal manure and organic soil amendments as an alternative to expensive inorganic fertilizers is becoming more prevalent in the USA and worldwide. A field experiment was conducted on Bluegrass–Maury silty loam soil at the Kentucky State University Research Farm using the Kennebec variety of white potato (Solanum tuberosum) under Kentucky climatic conditions. The study involved 12 soil treatments in a randomized complete block design. The treatments included four types of animal manures (cow manure, chicken manure, vermicompost, and sewage sludge), biochar at three application rates (5%, 10%, and 20%), and native soil as control plots. Additionally, animal manures were supplemented with 10% biochar to assess the influence of combining biochar with animal manure on the accumulation of heavy metals in potato tubers. The study aimed to (1) determine the concentration of seven heavy metals (Cd, Cr, Ni, Pb, Mn, Zn, Cu) and two essential nutrients (K and Mg) in soils treated with biochar and animal manure, and (2) assess metal mobility from soil to potato tubers at harvest by determining the bioaccumulation factor (BAF). The results revealed that Cd, Pb, Ni, Cr, and Mn concentrations in potato tubers exceeded the FAO/WHO allowable limits. Whereas the BAF values varied among the soil treatments, with Cd, Cu, and Zn having high BAF values (>1), and Pb, Ni, Cr, and Mn having low BAF values (<1). This observation demonstrates that potato tubers can remediate Cd, Cu, and Zn when grown under the soil amended with biochar and animal manure. Full article

Objectives: In this study, we aimed to evaluate the accuracy of four radiological methods for dental age estimation and to test which method is the most reliable in Montenegrin children. Methods: To determine dental age, we examined 351 panoramic radiographs of 190 female and 161 male children between the ages of 6 and 12 using the Demirjian method, Willems method, the European formula, and the BAF. The estimated dental age was compared with the chronological age, and the average, absolute, and standard deviations were calculated. Results: When comparing dental age to chronological age in females, overestimation occurred when using the Demirjian and Willems methods, whereas the European formula and the BAF resulted in underestimations. Only the European formula underestimated dental age in males, while the other three methods caused overestimations in comparison to chronological age. The European formula and the BAF revealed that, when all age groups were included, approximately 57.1–61% of patients deviated from their chronological age by less than six months. When using Demirjian’s method, nearly 30–35% of patients had dental ages that were either overestimated or underestimated by more than a year. Conclusions: The most accurate method for estimating the dental age of children under 13 in the Montenegrin population is the European formula. The Demirjian method had the lowest accuracy, whereas that in the BAF and the Willems method was similar. Full article

The BCR-ABL1 chimeric oncoprotein plays a pivotal role in the pathogenesis of Chronic Myeloid Leukemia (CML) as its constitutive kinase activity transforms the hematopoietic stem cell, promoting pro-survival signaling. We and others have previously shown that the manipulation of BCR-ABL1 catalytic activity modulates its intracellular localization, thereby transforming the culprit of CML into a pro-apoptotic protein that selectively kills leukemic cells. Here, we investigated the role of the BCR coiled-coil and C2 domains on BCR-ABL1 intracellular localization and leukemogenic potential. We performed a bioinformatic analysis that identified two putative nuclear localization signals (NLSs) in BCR. Using recombinant DNA strategies, we generated multiple BCR and BCR-ABL1 mutants that were ectopically expressed in human cells. The intracellular localization of each construct was analyzed by immunofluorescence, while their biological activity was investigated employing proliferation and transforming assays. We show that BCR displays two nuclear localization signals functionally inactivated by the coiled-coil and C2 domains. The removal of these regions reactivated the nuclear migration of both BCR and BCR-ABL1 mutants. Moreover, BCR-ABL1 constructs devoid of the coiled-coil and C2 domains displayed reduced transforming potential in Ba/F3 cells and in primary human CD34+ progenitors. Finally, we demonstrate that the deletion of the C2 domain compromises TKI efficacy. Our findings identify two nuclear localization signals in the BCR sequence that are functionally suppressed by the coiled-coil and C2 domains. Targeting these regions may provide additional therapeutic strategies to manipulate both BCR-ABL1 intracellular localization and kinase activity. Full article

Background/Objectives: ALK+ Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma that is characterized by expression of the Anaplastic Lymphoma Kinase (ALK), which is induced by the t(2;5) chromosomal rearrangement, leading to the expression of the NPM-ALK fusion oncogene. Most previous preclinical models of ALK+ ALCL were based on overexpression of the NPM-ALK cDNA from heterologous promoters. Due to the enforced expression, this approach is prone to artifacts arising from synthetic overexpression, promoter competition and insertional variation. Methods: To improve the existing ALCL models and more closely recapitulate the oncogenic events in ALK+ ALCL, we employed CRISPR/Cas-based chromosomal engineering to selectively introduce translocations between the Npm1 and Alk gene loci in murine cells. Results: By inducing precise DNA cleavage at the syntenic loci on chromosome 11 and 17 in a murine IL-3-dependent Ba/F3 reporter cell line, we generated de novo Npm-Alk translocations in vivo, leading to IL-3-independent cell growth. To verify efficient recombination, we analyzed the expression of the NPM-ALK fusion protein in the recombined cells and could also show the t(11;17) in the IL-3 independent Ba/F3 cells. Subsequent functional testing of these cells using an Alk-inhibitor showed exquisite responsiveness towards Crizotinib, demonstrating strong dependence on the newly generated ALK fusion oncoprotein. Furthermore, a comparison of the gene expression pattern between Ba/F3 cells overexpressing the Npm-Alk cDNA with Ba/F3 cells transformed by CRISPR-mediated Npm-Alk translocation indicated that, while broadly overlapping, a set of pathways including the unfolded protein response pathway was increased in the Npm-Alk overexpression model, suggesting increased reactive changes induced by exogenous overexpression of Npm-Alk. Furthermore, we observed clustered expression changes in genes located in chromosomal regions close to the breakpoint in the new CRISPR-based model, indicating positional effects on gene expression mediated by the translocation event, which are not part of the older models. Conclusions: Thus, CRISPR-mediated recombination provides a novel and more faithful approach to model oncogenic translocations, which may lead to an improved understanding of the molecular pathogenesis of ALCL and enable more accurate therapeutic models of malignancies driven by oncogenic fusion proteins. Full article

Artisanal small-scale gold mining (ASGM) is the largest source of global mercury (Hg) emissions. This study investigated Hg contamination in water, soil, sediment, fish, and cassava plants around ASGM sites in Gunung Pongkor, West Java, Indonesia. Hg concentration ranged from 0.06 to 4.49 µg/L in water; 0.420 to 144 mg/kg dw in soil; 0.920 to 150 mg/kg dw in sediment; 0.259 to 1.23 mg/kg dw in fish; 0.097 to 5.09 mg/kg dw in cassava root; and 0.350 to 8.84 mg/kg dw in cassava leaf. Geo-accumulation index (Igeo) analysis revealed moderate to heavy soil contamination upstream, likely due to direct ASGM input. In contrast, sediment Igeo values indicated heavy contamination downstream, suggesting Hg transport and sedimentation. Bioconcentration factors (BCFs) in fish were predominantly high in downstream and midstream areas, indicating enhanced Hg bioavailability. Bioaccumulation factors (BAFs) in cassava were higher in upstream areas. Health risk assessment, based on the Hazard Quotient (HQ) and Hazard Index (HI), identified ingestion as the primary exposure route, with children exhibiting significantly higher risks than adults. These findings highlight the significant Hg contamination associated with ASGM in Gunung Pongkor and emphasize the need for targeted mitigation strategies to protect human and environmental health. Full article

6-Aryl-7H-pyrrolo[2,3-d]pyrimidin-4-amines have promising properties as colony-stimulating factor 1 receptor (CSF1R) inhibitors. Inspired by these antagonists, two series of 1,2,3-triazole analogues (28 compounds) were synthesized and evaluated as CSF1R inhibitors. Enzymatic IC₅₀ profiling showed that 27 of the 28 derivatives had lower IC₅₀ than the reference drug PLX-3397. Three derivatives displayed CSF1R Ba/F3 cellular IC₅₀ well below 1 µM. Profiling of the most promising triazole analogue (compound 27a) toward a panel of kinases reveals a high selectivity for CSF1R with respect to its family kinases, but 27a also inhibits ABL, SRC, and YES kinases. Molecular docking of 27a toward two CSF1R X-ray structures identified two different ligand-inverted binding poses, which triggers interest for further investigations. Full article

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy associated with a poor prognosis. Activating mutations in the FLT3 gene occur in approximately 30% of AML cases, with internal tandem duplications in the juxtamembrane domain (FLT3-ITD; 75%) and mutations in the tyrosine kinase domain (FLT3-TKD; 25%). FLT3-ITD mutations are linked to poor prognosis and offer significant clinical predictive value, whereas the implications of FLT3-TKD mutations are less understood. The Hedgehog–Gli pathway is an established therapeutic target in AML, and emerging evidence suggests crosstalk between FLT3-ITD signaling and Gli expression regulation via non-canonical mechanisms. Post-translational modifications involving myristic and palmitic acids regulate various cellular processes, but their role in AML remains poorly defined. In this study, we investigated the role of fatty acid synthase (FASN), which synthesizes myristic and palmitic acids and catalyzes palmitoyl-acyltransferation, in regulating FLT3-ITD-Gli signaling. FASN knockdown using shRNA and the FASN inhibitor TVB-3166 was performed in FLT3-ITD-mutated AML cell lines (MOLM13, MV411) and Baf3-FLT3-ITD cells. The impact of FASN inhibition was assessed through Western blot and kinome profiling, while biological implications were evaluated by measuring cell viability and proliferation. FASN inhibition resulted in reduced levels of phospho-Akt (pAkt) and phospho-S6 kinase (pS6) and decreased expression of Hedgehog–Gli1, confirming non-canonical regulation of Gli by FLT3-ITD signaling. Combining TVB-3166 with the Gli inhibitor GANT61 significantly reduced the survival of MOLM13 and MV411 cells. Full article

The bivariate fertilizer applicator (BAF) is a crucial device for precision agriculture, and the optimization of the control sequence optimization (CSO) significantly impacts the performance of variable-rate fertilization (VRF). This study investigates the CSO problem as a multi-objective optimization problem (CSO-MOP) for BFA through the lens of balanced trade-offs among conflicting objectives, including fertilization accuracy, uniformity, and adjustment rapidity. We employed three multi-objective evolutionary algorithms (MOEAs), including NSGA-III, MOEAD-D, and AR-MOEA. To investigate the problem, we solved several instances for different target fertilization rates and selected appropriate evaluation metrics. Finally, we obtained the Pareto set (PS) from each MOEA and conducted a comparative analysis, including the performance of each algorithm in addressing the CSO-MOP, the conflicts between each pair of objectives, and the effects of the optimized control sequences derived from each algorithm on the three objectives. Full article

This study investigated the effects of acrylamide on the growth, neurobehavioral responses, gut integrity, microbial composition, and toxicokinetics of black soldier fly larvae (BSFL). Larvae were exposed to acrylamide-contaminated diets at 0.05, 0.5, and 5 mg/kg (dry weight) to assess dose-dependent impacts. Results revealed that acrylamide exposure delayed larval growth peaks and reduced maximum weights by 6.17–76.01% (12–18 days). Additionally, crawling speed decreased significantly at ≥0.5 mg/kg, indicating neurotoxicity. Trypan blue staining demonstrated dose-dependent midgut damage (2.22% in control vs. 25.56% at 5 mg/kg), correlating with compromised nutrient absorption. Gut microbiota analysis showed enrichment of pathogenic genera (e.g., Escherichia-Shigella) and suppression of beneficial taxa (e.g., Klebsiella), alongside reduced metabolic and immune-related pathways via Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Toxicokinetic modeling revealed bioaccumulation, with bioaccumulation factors (BAF) inversely related to substrate concentration (18.67 at 0.05 mg/kg vs. 2.90 at 5 mg/kg). Elimination half-lives (DT₅₀) varied from 3.25 to 8.22 days, suggesting concentration-dependent detoxification efficiency. These findings highlight acrylamide’s multifaceted toxicity in BSFL, emphasizing risks in waste valorization and insect-based feed production. This study underscores the need for substrate safety protocols to ensure sustainable applications of BSFL in the circular bioeconomy. Full article

A soluble photosensitive polyamide ester precursor (BAFPAE) was synthesized through copolymerization of 2,2-bis [4-(4-aminophenoxy)phenyl]hexafluoropropane (HFBAPP) with 4,4′-(4,4′-isopropylidenediphenoxy)bis(phthalic anhydride) (BPADA). Hydroxyethyl methacrylate (HEMA) was incorporated as a photosensitive functional group, and a transparent photosensitive polyimide film was obtained by thermal curing of the precursor film. The effects of reaction temperature and varying HEMA equivalents on the mechanical properties of the film were systematically investigated. The results indicated that the formation of polyacrylate-polyimide interpenetrating polymer networks (IPNs) was pivotal in preserving the mechanical integrity of the material. The optimized BAF-x-y exhibited a toughness of 12.69 MJ m³, a Young’s modulus of 2.86 GPa, an elongation at break of 21.16%, and a tensile strength of 92.68 MPa. Full article

Soil has the ability to serve as a universal sink, meaning it may absorb contaminants from the environment. Additionally, plant leaves can also be used as indicators of environmental contamination. In our study, the bioaccumulation factor (BAF) was used to assess metal accumulation in the soil and leaves of the neem tree (Azadirachta indica) in Faisalabad, Pakistan. We analyzed the primary physical and chemical characteristics of the surface layer of soil in urban, suburban, and rural areas along an urbanization gradient. The ICP-OES technique was used to analyze the following elements: Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr and Zn. The highest concentration of all elements was found in soil samples from urban areas, with an increasing tendency along with the urbanization gradient. A significant difference was found along the urbanization gradient on the plant leaves except for Cd, Cu, and Zn; a high level of pollution was measured for Ba, Pb, Co, Ni, Cr, and Cd in the urban area. We also calculated the bioaccumulation factor (BAF), but no clear pattern was found. Our findings show that high concentrations in soil do not always turn into higher plant uptake for plants. Our findings suggest that traffic and industrial emissions are likely the main cause of the metals in Faisalabad, because their concentration is higher than their background concentration. Our results also suggest that elemental analysis of soil and plant leaves is an appropriate indicator of environmental contamination. Full article

Food waste containing meat and fish presents a considerable environmental challenge due to regulatory constraints preventing its use in industrial insect farming. Although substrates derived from meat and fish are not currently approved for industrial insect feed production due to regulatory constraints, this study explores their potential in bioconversion through Hermetia illucens larvae. In this study, five different former foodstuffs containing meat and/or fish were tested to evaluate their suitability for BSFL rearing. The substrates included pizza with salami (PIZZA), cheeseburger (CHB), pasta Bolognese with meat (PASTA), chicken salad (CHISA), and fish salad (FISA). Results showed that BSFL successfully developed on all tested substrates. The highest performance was observed for FISA, with a total larval weight of 35.21 ± 3.91 g, dry matter yield of 11.21 ± 0.45 g, survival rate of 96.63 ± 0.40%, and the most efficient feed conversion ratio (FCR, 4.11 ± 0.59). Heavy metal analysis revealed substantial bioaccumulation of lead (Pb) and cadmium (Cd) in larvae. In particular, larvae reared on PIZZA showed a Pb concentration of 4.68 μg/100 g, with a corresponding bioaccumulation factor (BAF) of approximately 1.5. Cadmium accumulation was most notable in larvae fed CHB, with a Cd concentration of 0.41 ± 0.33 μg/100 g and a BAF of about 2.1. Despite this bioaccumulation, all detected concentrations remained well below the regulatory limits set by the European Union for animal feed, indicating not only the feasibility of H. illucens larvae in sustainable waste management but also its use as a safe protein source in animal feed. This research highlights the viability of integrating such food waste into insect bioconversion systems. With appropriate risk management, this practice could significantly improve nutrient recycling, waste management, and the circular economy, urging a regulatory review to allow broader substrate utilization. These positive outcomes underscore the potential of integrating currently restricted animal-derived food waste streams into H. illucens-based bioconversion systems, unlocking additional value for the circular economy and contributing to more efficient waste management practices. Full article

Cadmium is a non-essential element for proper plant growth and development and is highly toxic to humans and animals, in part because it inters with calcium-dependent processes in living organisms. For this reason, a study was conducted to assess the potential for producing maize (Zea mays) biomass in cadmium-contaminated soil for energy purposes. The energy potential of Zea mays was evaluated by determining the heat of combustion (Q), heating value (Hv), and the amount of energy produced from the biomass. Starch, compost, fermented bark, humic acids, molecular sieve, zeolite, sepiolite, expanded clay, and calcium carbonate were assessed as substances supporting biomass production from Zea mays. The accumulation and redistribution of cadmium in the plant were also investigated. The study was conducted in a vegetation hall as part of a pot experiment. Zea mays was grown in uncontaminated soil and in soil contaminated with 15 mg Cd²⁺ kg⁻¹. A strong toxic effect of cadmium on the cultivated plants was observed, causing a 62% reduction in the biomass of aerial parts and 61% in the roots. However, it did not alter the heat of combustion and heating value of the aerial part biomass, which were 18.55 and 14.98 MJ kg⁻¹ d.m., respectively. Of the nine substances tested to support biomass production, only four (molecular sieve, compost, HumiAgra, and expanded clay) increased the yield of Zea mays grown in cadmium-contaminated soil. The molecular sieve increased aerial part biomass production by 74%, compost by 67%, expanded clay by 19%, and HumiAgra by 15%, but none of these substances completely eliminated the toxic effects of cadmium on the plant. At the same time, the bioaccumulation factor (BAF) of cadmium was higher in the roots (0.21–0.23) than in the aerial parts (0.04–0.03), with the roots showing greater bioaccumulation. Full article