PRL2 phosphatase enhances oncogenic FLT3 signaling via dephosphorylation of the E3 ubiquitin ligase CBL at tyrosine 371.

Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. FMS-like tyrosine kinase receptor-3 (FLT3) is one of the major oncogenic receptor tyrosine kinases aberrantly activated in AML. Although protein tyrosine phosphatase PRL2 is highly expressed in some subtypes of AML compared with normal human hematopoietic stem and progenitor cells, the mechanisms by which PRL2 promotes leukemogenesis are largely unknown. We discovered that genetic and pharmacological inhibition of PRL2 significantly reduce the burden of FLT3-internal tandem duplications-driven leukemia and extend the survival of leukemic mice. Furthermore, we found that PRL2 enhances oncogenic FLT3 signaling in leukemia cells, promoting their proliferation and survival. Mechanistically, PRL2 dephosphorylates the E3 ubiquitin ligase CBL at tyrosine 371 and attenuates CBL-mediated ubiquitination and degradation of FLT3, leading to enhanced FLT3 signaling in leukemia cells. Thus, our study reveals that PRL2 enhances oncogenic FLT3 signaling in leukemia cells through dephosphorylation of CBL and will likely establish PRL2 as a novel druggable target for AML.

Adsorption and leaching of fluorotelomer compounds and perfluoroalkyl acids in aqueous media by activated carbon prepared from municipal biosolids.

Perfluoroalkyl acids (PFAAs) are ubiquitous in nature and pose serious health risks to humans and animals. Limiting PFAA exposure requires novel technology for their effective removal from water. We investigated the efficacy of biosolid-based activated carbon (Bio-SBAC) in removing frequently detected PFAAs and their precursor fluorotelomer compounds at environmentally relevant concentrations (∼50 µg/L). Batch experiments were performed to investigate adsorption kinetics, isotherms, and leachability. Bio-SBAC achieved >95% removal of fluorotelomeric compounds, indicating that the need for PFAA removal from the environment could be minimised if the precursors were targeted. Kinetic data modelling suggested that chemisorption is the dominant PFAA adsorption mechanism. As evidenced by the isotherm modelling results, Freundlich adsorption intensity, n-1, values of <1 (0.707-0.938) indicate chemisorption. Bio-SBAC showed maximum capacities for the adsorption of perfluorooctanoic acid (1429 µg/g) and perfluorononanoic acid (1111 µg/g). Batch desorption tests with 100 mg/L humic acid and 10 g/L NaCl showed that Bio-SBAC effectively retained the adsorbed PFAA with little or no leaching, except perfluorobutanoic acid. Overall, this study revealed that Bio-SBAC is a value-added material with promising characteristics for PFAA adsorption and no leachability. Additionally, it can be incorporated into biofilters to remove PFAAs from stormwater, presenting a sustainable approach to minimise biosolid disposal and improve the quality of wastewater before discharge into receiving waters.

Therapy-related myeloid neoplasms resembling juvenile myelomonocytic leukemia: a case series and review of the literature.

Therapy-related myeloid neoplasms (t-MN) are a distinct subgroup of myeloid malignancies with a poor prognosis that include cases of therapy-related myelodysplastic syndrome (t-MDS), therapy-related myeloproliferative neoplasms (t-MPN) and therapy-related acute myeloid leukemia (t-AML). Here, we report a series of patients with clinical features consistent with juvenile myelomonocytic leukemia (JMML), an overlap syndrome of MDS and myeloproliferative neoplasms that developed after treatment for another malignancy.

Microplastic removal from urban stormwater: Current treatments and research gaps.

Stormwater is a major contributor to microplastic (MP) pollution in the aquatic environment. Although MPs are associated with many toxicological effects, their levels in stormwater are not regulated. This review compared the effectiveness of different MP removal technologies from stormwater runoff and examined the performance of typical stormwater treatment systems for MP removal to assess possible MP pollution control via stormwater management. Bioretention and filtration systems performed similarly with 84-96% MP removal efficiencies. Despite the limited number of studies that focused on wetlands and retention ponds, preliminary data suggested potential for MP removal with efficiencies of 28-55% and 85-99%, respectively. Despite the higher efficiency of bioretention and filtration systems, their removal efficiency of fibrous MPs was not optimal. Furthermore, wetlands were less effective in removing MPs than retention ponds, although the limited data might lead to an inaccurate representation of typical performances. Therefore, more research is required to arrive at definitive conclusions and to investigate alternative treatment options, such as ballasted sand flocculation, flotation, and biological degradation, and evaluate the effectiveness of bioretention and filtration for MPs <100 µm.

Adsorption of p-benzoquinone at low concentrations from aqueous media using biosolid-based activated carbon.

The toxic oxidation intermediate p-benzoquinone exists in aqueous environments at dilute concentrations above the fish-toxicity limit of 0.045 mg/L, affecting aquatic life. The reduction of this compound to the concentrations required to achieve safe discharge limits is challenging. In this study, the adsorptive removal of p-benzoquinone by a biosolid-based activated carbon (SBAC) was systematically investigated in batch experiments. The adsorption rate was rapid, and the bulk of p-benzoquinone adsorption occurred within 30 min. The maximum adsorption capacity of SBAC was estimated at 19.6 mg/g using the Langmuir isotherm model. Its adsorptivity was independent of temperature from 6 to 40 °C. The presence of 6 g/L of chloride and 500 mg/L of sulphate did not affect the removal of 1 mg/L p-benzoquinone, whereas 15 mg/L of humic acid media slightly decreased the p-benzoquinone removal from 87.0% to 83.2%. Diffusion, hydrophilic, and electrostatic interactions (i.e., dipole-dipole) govern the adsorption of p-benzoquinone and are influenced by the SBAC surface chemistry. Biosolid-based activated carbon can lower the residual p-benzoquinone to below the fish-toxicity limit of 0.045 mg/L within 1 h of sequential adsorption. Thus, biosolid-based activated carbon can effectively remove p-benzoquinone from aqueous environments; this is a waste-to-resource approach that addresses sustainability (waste disposal) and environmental protection (pollutant removal).

Removal of polycyclic aromatic hydrocarbons from aqueous media using modified clinoptilolite.

Carcinogenic polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment. In this study, the removal of PAHs from aqueous media was assessed using samples of clinoptilolite, a natural zeolite, pre-treated with 1 mol/L of NaCl, (Na pre-treated clinoptilolite, NC). Samples (10 g) of NC were separately modified with 5, 2, 2, and 20-mmol/L solutions of cetylpyridinium chloride (CPC), didodecyldimethyl ammonium bromide (DDAB), hexadecyltrimethylammonium bromide (HDTMA), and tetramethyl ammonium chloride (TMA) surfactants as potential cost-effective adsorbents. The kinetics, optimal sorbent dosage, and competitive effects were evaluated through batch adsorption tests using deionised water spiked with five PAHs (anthracene (50 µg/L), fluoranthene (100 µg/L), fluorene (100 µg/L), phenanthrene (100 µg/L), and pyrene (100 µg/L)). The surfactant non-modified (NC) and TMA-MC (modified clinoptilolite) exhibited PAH removal of <66% from the spiked concentration in aqueous solution, while CPC-MC, DDAB-MC, and HDTMA-MC achieved removal rates of >93% for the five PAHs after 24 h at a solid:liquid ratio of 1:100. The remaining concentrations of anthracene and fluoranthene were below 3 µg/L, and that of fluorene was <6 µg/L, lower than the water quality criteria of British Columbia, Canada, for protecting aquatic life. However, HDTMA-MC retained >83% of the fluorene. Over 80% of all PAHs were absorbed within 15 min for the CPC-MC and DDAB-MC, and the maximum adsorption was reached in <2 h. Three kinetic models were applied assuming pseudo-first-order, pseudo-second-order, and intra-particle equations, and the results were well-represented by the pseudo-second-order equation. The PAH sorption results indicated that the adsorption mechanism is based on PAH hydrophobicity, and π-π electron-donor-acceptor interaction with surfactant. CPC and DDAB with two long chain hydrocarbons had more PAH adsorption than HDTMA with one, and TMA with no long chain hydrocarbons (DDAB-MC > CPC-MC > HDTMA-MC â‰« TMA-MC > NC). With a solid:liquid ratio of 1:200, over 90%, 80%, and 70% of the anthracene, fluoranthene, and pyrene were adsorbed by the CPC-MC, DDAB-MC, and HDTMA-MC, respectively.

Simultaneous removal of polycyclic aromatic hydrocarbons and heavy metals from natural soil by combined non-ionic surfactants and EDTA as extracting reagents: Laboratory column tests.

Simultaneous removal of three polycyclic aromatic hydrocarbons (acenaphthene, fluorene and fluoranthene) co-existing with three heavy metals (Ni, Pb and Zn) in artificially contaminated soil from the vicinity of an oil refinery was examined by column flushing of solutions containing Triton X-100 + Ethylenediaminetetraacetic acid (EDTA) and Tween 80 + EDTA at three levels of surfactant concentrations. While the effectiveness of both combined solutions in removal of heavy metals did not differ significantly, Triton X-100 + EDTA was more efficient in removing PAHs. Results showed that after 21 pore volume flushing of enhancing solution (Triton X-100 7.5% + EDTA 0.01 M) at flow rate of 0.534 mL min-1 through the column with hydraulic conductivity of 8.5 × 10-5 cm s-1, 54, 47 and 40% of acenaphthene, fluorene, and fluoranthene were removed simultaneously. At the same conditions, 75, 85 and 90% of Pb, Ni and Zn, were also simultaneously removed. Increasing the flow rate of flushing solution decreased the removal efficiency of the contaminants.

Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications.

BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1-like ALL cases and used their expression values - assessed by quantitative real time-polymerase chain reaction (Q-RT-PCR) in 26 BCR/ABL1-like and 26 non-BCR/ABL1-like cases to build a statistical "BCR/ABL1-like predictor", for the identification of BCR/ABL1-like cases. By screening 142 B-lineage ALL patients with the "BCR/ABL1-like predictor", we identified 28/142 BCR/ABL1-like patients (19·7%). Overall, BCR/ABL1-like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1-like cases identified by the BCR/ABL1-like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event-free survival (P = 0·0009) compared to non-BCR/ABL1-like ALL. Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. We propose a simple tool based on Q-RT-PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1-like ALL cases at diagnosis.

Exploratory study on modification of sludge-based activated carbon for nutrient removal from stormwater runoff.

Nutrients (P, N) in stormwater runoff are a major cause of eutrophication and algal blooms. A promising solution to this problem is to amend the rain garden growing medium (RGGM) with sewage sludge-based activated carbon (SBAC). To optimize the SBAC production process, different metals, pyrolysis conditions (temperature, heating time, carrier gas), and post-treatments were explored. When pyrolyzed at 400 °C for two hours, Zn-activated SBAC removed up to 41% of PO4-P (initial concentration of 1 mg/L) and 72% of NO3-N (initial concentration of 2 mg/L), at a dose of 1 g sorbent/L of nutrient-spiked distilled water. When the same dosage was applied to stormwater leachate made from RGGM and spiked with nutrients, the removal efficiencies were reduced to 20% for PO4-P and 38% for NO3-N. These reductions were probably caused by competition from other leachate components. Increasing the dosage to 3 g/L leachate improved PO4-P removal to 31% and NO3-N to 72%, while also resulting in the removal of 46% of total organic carbon. The major energy cost of producing such sorbents is estimated to be ∼$0.76 CAD/kg SBAC.

Desorption and mobility mechanisms of co-existing polycyclic aromatic hydrocarbons and heavy metals in clays and clay minerals.

The effects of soil components such as clay minerals and as humic acids, as well as co-existing metals and polycyclic aromatic hydrocarbons, on desorption and mobility are examined. Three types of artificially blended clay and clay mineral mixtures (pure kaolinite, kaolinite + sand and kaolinite + sand + bentonite), each with different humic acid content, were tested for desorption and mobility of acenaphthene, fluorene and fluoranthene by three extracting solutions CaCl2 (0.01 M) and EDTA (0.01M) with non-ionic surfactants (Tween 80 and Triton X100). Heavy metals (Ni, Pb and Zn) were also studied for desorption and mobility. The influence of co-present metals on simultaneous desorption and mobility of PAHs was investigated as well. The results showed that <10% of metals in the clay mineral mixtures were mobile. Combined EDTA and non-ionic solutions can enhance the desorption and mobility of PAHs to >80% in clay mineral mixtures containing no sand, while in the same soils containing ∼40% sand, the desorption exceeded 90%. Heavy metals, as well as increasing humic acids content in the clay mineral mixtures, decreased the desorption and mobility of PAHs, especially for soils containing no sand, and for fluoranthene compared with fluorene and acenaphthene.

Adsorption of organic stormwater pollutants onto activated carbon from sewage sludge.

Adsorption filters have the potential to retain suspended pollutants physically, as well as attracting and chemically attaching dissolved compounds onto the adsorbent. This study investigated the adsorption of eight hydrophobic organic compounds (HOCs) frequently detected in stormwater - including four polycyclic aromatic hydrocarbons (PAHs), two phthalates and two alkylphenols - onto activated carbon produced from domestic sewage sludge. Adsorption was studied using batch tests. Kinetic studies indicated that bulk adsorption of HOCs occurred within 10 min. Sludge-based activated carbon (SBAC) was as efficient as tested commercial carbons for adsorbing HOCs; adsorption capacities ranged from 70 to 2800 µg/g (Cinitial = 10-300 µg/L; 15 mg SBAC in 150 mL solution; 24 h contact time) for each HOC. In the batch tests, the adsorption capacity was generally negatively correlated to the compounds' hydrophobicity (log Kow) and positively associated with decreasing molecule size, suggesting that molecular sieving limited adsorption. However, in repeated adsorption tests, where competition between HOCs was more likely to occur, adsorbed pollutant loads exhibited strong positive correlation with log Kow. Sewage sludge as a carbon source for activated carbon has great potential as a sustainable alternative for sludge waste management practices and production of a high-capacity adsorption material.

Sorption of DOM and hydrophobic organic compounds onto sewage-based activated carbon.

Treatment of stormwater via sorption has the potential to remove both colloidal and dissolved pollutants. Previous research shows that activated carbon produced from sewage sludge is very efficient in sorbing hydrophobic organic compounds (HOCs), frequently detected in stormwater. The aim of this research was to determine whether the presence of dissolved organic matter (DOM) has a negative effect on the adsorption of HOCs onto sludge-based activated carbon (SBAC) in batch adsorption tests. Batch adsorption tests were used to investigate the influence of two types of DOM - soil organic matter and humic acid (HA) technical standard - on the sorption of HOCs onto SBAC, and whether preloading adsorbent and adsorbates with DOM affects HOC sorption. The results indicate that soil DOM and HAs do not have a significant negative effect on the adsorption of HOCs under tested experimental conditions, except for a highly hydrophobic compound. In addition, preloading SBAC or HOCs with DOM did not lead to lower adsorption of HOCs. Batch adsorption tests appear to be inefficient for investigating DOM effects on HOC adsorption, as saturating the carbon is difficult because of high SBAC adsorption capacity and low HOC solubility, so that limited competition occurs on the sorbent.

Compositional effects on leaching of stain-guarded (perfluoroalkyl and polyfluoroalkyl substance-treated) carpet in landfill leachate.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) from stain-guard treated carpets in landfills continue to be released into the environment. To understand the leaching of PFASs from carpets to landfill leachate as a function of environmental factors, leaching concentrations of ten perfluoroalkyl carboxylic acids and four perfluoroalkyl sulfonic acids were quantified for different pHs, contact times, mixing speeds, and temperatures. Partitioning from carpet to leachate and distilled water at different pHs showed negligible differences. The total concentration of leaching PFASs in distilled water was approximately 1 ng L(-1) higher than in landfill leachate, indicating that the presence of multivalent cations in leachate could have a negative effect on leaching of PFASs. For all PFASs monitored, leaching increased with increasing contact time and temperature. Perfluorohexanoic and perfluoroheptanoic acids experienced the largest increases with contact time and temperature. Gibbs free energy (ΔG > 0), enthalpy (ΔH > 0), and entropy energy (ΔS < 0) indicated that PFAS leaching from carpet was dominantly controlled by entropy-driven processes and did not differ significantly among individual PFASs. PFAS concentrations in leachate with rotation of an end-over-end contactor were higher than under static conditions, but otherwise, varying the rotation speed had negligible influence. The results provide useful information for management of discarded stain-guard carpets in landfills.

Evaluation of low-cost materials for sorption of hydrophobic organic pollutants in stormwater.

Conventional stormwater treatment techniques such as sedimentation and filtration are inefficient for removing the dissolved and colloidal phases of hydrophobic organic compounds (HOCs) present in stormwater. Adsorption could be a promising technique for removing colloidal and dissolved pollutants. Five low-cost sorbent materials were investigated in this project, including two minerals ­ vermiculite and perlite ­ and three waste products ­ two pine barks and a sawdust ­ as potential adsorbents for removal of polycyclic aromatic hydrocarbons (PAHs), alkylphenols and phthalates; HOCs commonly found in stormwater. Adsorption capacity and kinetics were studied through batch adsorption tests using synthetic stormwater spiked with a mixture of HOCs. Vermiculite and perlite exhibited insignificant removal of the organic contaminants. The three wood-based materials retained >80% of the initial HOC concentration (10-300 µg/L). The two barks exhibited slightly higher adsorption capacities of HOCs than the sawdust. For all compounds tested, maximum adsorption onto the wood-based media was reached in <10 min. The highest adsorption capacity was found for PAHs (up to 45 µg/g), followed by alkylphenols and phthalates. No correlation was found between adsorption capacity and physical-chemical parameters such as solubility and partition coefficients (log K(ow)). Agreement between empirical data and the pseudo-second order kinetic model suggest chemisorption of HOCs onto a monolayer on wood-based media. This could lead to early saturation of the materials and should be investigated in future studies through repeated adsorption of HOCs, for example in column studies.

Adsorption and hydraulic conductivity of landfill-leachate perfluorinated compounds in bentonite barrier mixtures.

Perfluorinated compounds (PFCs) are leached in landfills from a wide range of domestic and industrial products. Sodium bentonite, a common barrier material, was contacted with water and landfill leachate spiked with PFCs in batch adsorption tests to measure PFC adsorption. Leaching cell tests were also conducted in which water, landfill leachate and PFC-spiked leachate permeated through compacted sand-bentonite mixtures. It was found that the PFCs did not bind substantially to the bentonite. Hydraulic conductivities were not appreciably affected by the PFCs, showing that bentonite liners are not affected for the range of concentrations tested. The sand-bentonite mixture partially retained the PFCs, indicating limited effectiveness in containing PFC within landfills.

Assessment of metals pollution and health risk in dust from nursery schools in Xi'an, China.

Concentrations, pollution and health risks of metals in dust from nursery schools in Xi'an, China were determined. In comparison with local soil, dust samples have elevated metals concentrations except for Mn. The results indicate no distinct pollution of Mn, Ni, As and Ba in the dust, while Cu, Co and Zn are moderate pollution, Pb is significant pollution, and Cr with large pollution range. Most samples presented moderately polluted by metals. The non-cancer risks of the studied metals are within the safe range, and the cancer risks of As, Co, Cr and Ni are also within the currently acceptable range.

Co-pyrolysis of sewage sludge and biomass waste into biofuels and biochar: A comprehensive feasibility study using a circular economy approach.

Enormous annual sewage sludge (SS) volumes pose global environmental challenges owing to contamination and significant greenhouse gas emissions. Here, we investigated the economic viability of co-pyrolyzing SS and biomass waste to produce biofuels (bio-oil and gas) and biochar. Net present worth (NPW) analysis, the sale product break-even price, and sludge handling price (SHP) were used to determine the profitability of co-pyrolysis compared with SS pyrolysis alone and conventional treatment methods. In this study, the sale prices of biochar based on quality (i.e., stability, carbon sequestration effectiveness, and heavy metal content) were estimated to be 2.24, 1.44, and 0.98 CAD/kg for high-, medium-, and low-grade biochar. The bio-oil prices, estimated based on the higher heating values of bio-oil and diesel, ranged from 0.80 to 1.22 CAD/kg. Sawdust (SD) and wheat straw (WS) were the chosen co-pyrolysis feedstocks, with four mixing ratios (20, 40, 60, and 80 wt%). Economically, SD (40 wt% mixing ratio) co-pyrolysis achieved the best performance, with a maximum NPW of 8.71 million CAD. SD single and co-pyrolysis were the only profitable scenarios. Moreover, SS single pyrolysis and WS co-pyrolysis exhibited higher profitability than conventional SS treatment methods, with SHPs of 65 and 40 CAD/1000 kg dry sludge, respectively. Sensitivity analysis highlighted the dependence of economic performance on biochar and bio-oil market value. This study offers the first economic analysis of this approach and enhances our understanding of the potential of co-pyrolysis for biofuel and biochar production, providing innovative solutions for the environmental challenges of SS disposal.

Removal of perfluoroalkyl acids from aqueous media by surfactant-modified clinoptilolites.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are environmentally persistent, bioaccumulating, and toxic compounds that have attracted global attention. It is challenging to reduce the residual concentrations of these compounds to safe discharge limits. In this study, batch experiments were performed to evaluate natural clinoptilolite and clinoptilolites modified (MC) with cetylpyridinium chloride (CPC-MC), didodecyldimethylammonium bromide (DDAB-MC), hexadecyltrimethylammonium bromide (HDTMA-MC), and tetramethylammonium chloride (TMA-MC) as cost-effective aqueous PFAS adsorbents. The removal capacities of the adsorbents for the majority of the PFASs decreased in the following order: DDAB-MC > CPC-MC ≫ modified natural clinoptilolite with hexadecyltrimethyl ammonium bromide (HDTMA-MC) ≫ modified natural clinoptilolite with tetramethylammonium chloride (TMA-MC) ≈ natural clinoptilolite modified with NaCl (NC). In particular, CPC-MC and DDAB-MC reduced PFASs concentration in 50 µg/L by up to 98% for perfluorooctane sulphonate. Within 30 min, CPC-MC (30.5 µg/L) and DDAB-MC (32.1 µg/L) met the PFOS water quality criterion of 36 µg/L in inland surface waters. Both adsorbents met this criterion at the highest solution volume (40 mL) and 0.125 g/L (solid-to-liquid ratio of 1:8). PFASs with short hydrocarbon chains competed more for adsorption. PFASs with sulphonate functional groups were also adsorbed more than carboxyl groups in single- and multi-PFAS solutions. The modified surfaces of clinoptilolites controlled PFAS adsorption through hydrophobic and electrostatic interactions. PFAS removal with surfactant-modified clinoptilolites is cost-effective and protects aquatic environments by using surplus natural materials.

PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation.

Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells. IMPLICATIONS: Our studies uncover a novel mechanism that fine-tunes oncogenic KIT signaling in leukemia cells and will likely identify PRL2 as a novel therapeutic target in AML with KIT mutations.