Degradation of Nitrobenzene by Mackinawite through a Sequential Two-Step Reduction and Oxidation Process.

Mackinawite (FeS) has gained increasing interest due to its potential application in contaminant removal by either reduction or oxidation processes. This study further demonstrated the efficiency of FeS in degrading nitrobenzene (ArNO2) via a sequential two-step reduction and oxidation process under neutral conditions. In the reduction stage, FeS rapidly reduced ArNO2 to aniline (ArNH2), with nitrosobenzene (ArNO) and phenylhydroxylamine (ArNHOH) serving as the intermediates. X-ray photoelectron spectroscopy (XPS) analysis indicated that both Fe(II) and S(II) in FeS contributed electrons to the reduction of ArNO2. In the subsequent oxidation stage with oxygen, by addition of 0.5 mM tripolyphosphate (TPP), ArNH2 generated in the reduction process could be effectively oxidized to aminophenols by hydroxyl radicals (•OH), which would undergo eventual mineralization via ring-cleavage reactions. TPP exerted a favorable role in enhancing •OH production for ArNH2 degradation by promoting the formation of the dissolved Fe(II)-TPP complex, thus enhancing the homogeneous Fenton reaction. Additionally, TPP adsorption inhibited the surface oxidation reactivity of FeS due to the change of Fe(II) coordination. Finally, the effective degradation of ArNO2 by FeS in actual groundwater was demonstrated by using this sequential reduction and oxidation approach. These research findings provide a theoretical basis for a new FeS-based remediation approach, offering an alternative way for comprehensive removal of ArNO2.

Mechanistic Insight into Electron Transfer from Fe(II)-Bearing Clay Minerals to Fe (Hydr)oxides.

Electron transfer (ET) is the essence of most biogeochemical processes related to element cycling and contaminant attenuation, whereas ET between different minerals and the controlling mechanism remain elusive. Here, we used surface-associated Fe(II) as a proxy to explore ET between reduced nontronite NAu-2 (rNAu-2) and Fe (hydr)oxides in their coexisting systems. Results showed that ET could occur from rNAu-2 to ferrihydrite but not to goethite, and the ET amount was determined by the number of reactive sites and the reduction potential difference between rNAu-2 and ferrihydrite. ET proceeded mainly through the mineral-mineral interface, with a negligible contribution of dissolved Fe2+/Fe3+. Control experiments by adding K+ and increasing salinity together with characterizations by X-ray diffraction, scanning electron microscopy/energy-dispersive spectrometry, and atomic force microscopy suggested that ferrihydrite nanoparticles inserted the interlayer space in rNAu-2 where structural Fe(II) in rNAu-2 transferred electrons mainly through the basal plane to ferrihydrite. This study implicates the occurrence of ET between different redox-active minerals through the mineral-mineral interface. As minerals at different reduction potentials often coexist in soils/sediments, the mineral-mineral ET may play an important role in subsurface biogeochemical processes.

Role of interfacial electron transfer reactions on sulfamethoxazole degradation by reduced nontronite activating H2O2.

It has been documented that organic contaminants can be degraded by hydroxyl radicals (•OH) produced by the activation of H2O2 by Fe(II)-bearing clay. However, the interfacial electron transfer reactions between structural Fe(II) and H2O2 for •OH generation and its effects on contaminant remediation are unclear. In this study, we first investigated the relation between •OH generation sites and sulfamethoxazole (SMX) degradation by activating H2O2 using nontronite with different reduction extents. SMX (5.2-16.9 µmol/L) degradation first increased and then decreased with an increase in the reduction extent of nontronite from 22% to 62%, while the •OH production increased continually. Passivization treatment of edge sites and structural variation results revealed that interfacial electron transfer reactions between Fe(II) and H2O2 occur at both the edge and basal plane. The enhancement on basal plane interfacial electron transfer reactions in a high reduction extent rNAu-2 leads to the enhancement on utilization efficiencies of structural Fe(II) and H2O2 for •OH generation. However, the •OH produced at the basal planes is less efficient in oxidizing SMX than that of at edge sites. Oxidation of SMX could be sustainable in the H2O2/rNAu-2 system through chemically reduction. The results of this study show the importance role of •OH generation sites on antibiotic degradation and provide guidance and potential strategies for antibiotic degradation by Fe(II)-bearing clay minerals in H2O2-based treatments.

Ligand-Enhanced Electron Utilization for Trichloroethylene Degradation by ·OH during Sediment Oxygenation.

The potential of oxygenating Fe(II)-bearing sediments for hydroxyl radical (·OH) production and contaminant degradation has been proposed recently. Here, we further show that specific ligands can largely enhance contaminant degradation during sediment oxygenation due to increased utilization efficiency of sediment electrons. With the addition of 0-2 mM sodium ethylene diamine tetraacetate (EDTA) or sodium tripolyphosphate (TPP) in sediment suspension (50 g/L, pH 7.0), trichloroethylene (TCE, 15 µM) degradation increased from 13% without ligand to a maximum of 80% with 2 mM TPP and was much higher with TPP than EDTA because EDTA competes for ·OH. Electron utilization efficiency for ·OH production increased with increased ligand concentration and was enhanced by up to 6-7 times with 2 mM EDTA or TPP. Electron transfer from sediment to dissolved Fe(III)-ligand is mainly accountable for the enhanced electron utilization efficiency by the ligands with low adsorption affinity (i.e., EDTA), and additional variation of sediment surface Fe(II) coordination is mainly responsible for the enhancement by the ligands with high adsorption affinity (i.e., TPP). Output of this study provides guidance and optional strategies for enhancing contaminant degradation during sediment oxygenation.

Characterization of Coprecipitates of As(III) and Fe(II) in the Presence of Phyllosilicate Nanoparticles.

Phyllosilicate nanoparticles play an important role in regulating the biogeochemical processes of Fe(II) and As(III) in paddy soils due to their high mobility and activity. In the present work, two prepared muscovite nanoparticles with different sizes (LNPs and SNPs) were used to investigate the effect of the size of phyllosilicate nanoparticles on the coprecipitation of Fe(II) and As(III) during oxidation process. The results showed that muscovite nanoparticles could significantly promote the removal of Fe(II) and As(III) during coprecipitation process. The formation of crystalline iron oxide and oxidation of As(III) tended to be suppressed by the two muscovite nanoparticles, and the suppression increased as muscovite nanoparticle size decrease. The findings of this study provide a contribution to understanding the roles of the natural phyllosilicate nanoparticles in regulating the biogeochemical processes of Fe and As elements in polluted paddy soils.

Oxidative Degradation of Organic Contaminants by FeS in the Presence of O2.

Reductive transformation of organic contaminants by FeS in anoxic environments has been documented previously, whereas the transformation in oxic environments remains poorly understood. Here we show that phenol can be efficiently oxidized in oxic FeS suspension at circumneutral pH value. We found that hydroxyl radicals (•OH) were the predominant reactive oxidant and that a higher O2 content accelerated phenol degradation. Phenol oxidation depended on •OH production and utilization efficiency, i.e., phenol degraded per •OH produced. Low FeS contents (≤1 g/L) produced less •OH but higher utilization efficiency, while high contents produced more •OH but lower utilization efficiency. Consequently, the most favorable conditions for phenol oxidation occurred during the long-term interaction between dissolved O2 and low levels of FeS (i.e., ≤1 g/L). Mössbauer spectroscopy suggests that FeS oxidation to lepidocrocite initially produced an intermediate Fe(II) phase that could be explained by the apparent preferential oxidation of structural S(-II) relative to Fe(II), rendering a higher initial •OH yield upon unit of Fe(II) oxidation. Trichloroethylene can be also oxidized under similar conditions. Our results demonstrate that oxidative degradation of organic contaminants during the oxygenation of FeS can be a significant but currently underestimated pathway in both natural and engineered systems.

Contaminant Degradation by •OH during Sediment Oxygenation: Dependence on Fe(II) Species.

It has been documented that contaminants could be degraded by hydroxyl radicals (•OH) produced upon oxygenation of Fe(II)-bearing sediments. However, the dependence of contaminant degradation on sediment characteristics, particularly Fe(II) species, remains elusive. Here we assessed the impact of the abundance of Fe(II) species in sediments on contaminant degradation by •OH during oxygenation. Three natural sediments with different Fe(II) contents and species were oxygenated. During 10 h oxygenation of 200 g/L sediment suspension, 2 mg/L phenol was negligibly degraded for sandbeach sediment (Fe(II): 9.11 mg/g), but was degraded by 41% and 52% for lakeshore (Fe(II): 9.81 mg/g) and farmland (Fe(II): 19.05 mg/g) sediments, respectively. •OH produced from Fe(II) oxygenation was the key reactive oxidant. Sequential extractions, X-ray diffraction, Mössbauer, and X-ray absorption spectroscopy suggest that surface-adsorbed Fe(II) and mineral structural Fe(II) contributed predominantly to •OH production and phenol degradation. Control experiments with specific Fe(II) species and coordination structure analysis collectively suggest the likely rule that Fe(II) oxidation rate and its competition for •OH increase with the increase in electron-donating ability of the atoms (i.e., O) complexed to Fe(II), while the •OH yield decreases accordingly. The Fe(II) species with a moderate oxidation rate and •OH yield is most favorable for contaminant degradation.

Effect of Coexisting Fe(III) (oxyhydr)oxides on Cr(VI) Reduction by Fe(II)-Bearing Clay Minerals.

Fe(II)-bearing clay minerals are important electron sources for Cr(VI) reduction in subsurface environments. However, it is not clear how iron (oxyhydr)oxides impact Cr(VI) reduction by Fe(II)-bearing clays as the two minerals can coexist in soil and sediment aggregates. This study investigated Cr(VI) reduction in the mixed suspensions of reduced nontronite NAu-2 (rNAu-2) and ferrihydrite (Fe(II)/Cr(VI) = 3:1). When the mineral premixing time increased from 0 to 72 h, Cr(VI) reduction was accelerated prominently in the initial stage, while Cr(VI) sorption was inhibited drastically. Mineral premixing led to electron transfer from structural Fe(II) in rNAu-2 to ferrihydrite with formation of reactive-surface-associated Fe(II), which catalyzed ferrihydrite transformation to lepidocrocite. Reactive-surface-associated Fe(II) accelerated Cr(VI) reduction initially, and ferrihydrite transformation to lepidocrocite was responsible for the inhibited sorption. When the reactive-surface-associated Fe(II) was consumed in the initial stage, the Cr(VI) reduction rate decreased dramatically due to the limitation of slow electron transfer from structural Fe(II) in rNAu-2 to surface-reactive sites. The main reduction sites shifted from rNAu-2 to ferrihydrite/lepidocrocite when rNAu-2 coexisted with ferrihydrite. Our findings demonstrate that electron transfer between minerals has important implications for Cr(VI) and other high-valence contaminant reduction by Fe(II)-bearing clay minerals in subsurface environments.

Therapeutic effect of human umbilical cord mesenchymal stem cells on tubal factor infertility using a chronic salpingitis murine model.

BACKGROUND: The study was conducted to evaluate the application of human umbilical cord mesenchymal stem cells (hUCMSCs) in the treatment of tubal factor infertility (TFI) caused by Chlamydia trachomatis, and investigate their effect on fertility in animal models of chronic salpingitis. METHODS: In this study, we investigated the therapy effects of the transplantation of hUCMSCs in tubal factor infertility using a chronic salpingitis murine model which induced Chlamydia trachomatis. Twenty rats were divided into two groups: control group (n = 10) and treatment group (n = 10). hUCMSCs were given to mice after exposure to C. trachomatis for 4 weeks. After treatment for 4 weeks, five mice were randomly selected from each of the two groups to sacrifice and we examined the organ morphology and pathology, inflammatory cytokines, proliferation, and apoptosis in fallopian tube (FT).The remaining five mice from each group were caged 2:1 with male mice for another 4 weeks, the numbers of pregnant mice and the mean number of pups in the different groups were enumerated and calculated. RESULTS: Intravaginal inoculation of hUCMSCs alleviated hydrosalpinx of the oviduct. EdU-labeled hUCMSCs are located at the interstitial site of the fallopian tube. Macrophage (F4/80) infiltration was significantly reduced in the treatment group compared with the control group and expression levels of the anti-inflammatory cytokine IL10 were increased after hUCMSCs treatment. Furthermore, mRNA and protein expression levels of PCNA and Caspase-3 were increased and decreased, respectively, in the hUCMSCs' treatment group compared with the control. Moreover, hUCMSCs' transplantation improved murine fertility. CONCLUSIONS: Anti-inflammatory and anti-apoptotic effects of hUCMSCs may play an important role in TFI. Our data suggest that hUCMSCs' transplantation contributed to the repair of tubal injury and improvement of fertility, providing a basis for assessing the contribution of stem cells in the oviduct for direct repair of the tube to assist reproduction.

Synthesis of Z-scheme g-C3N4-Ti(3+)/TiO2 material: an efficient visible light photoelectrocatalyst for degradation of phenol.

In this study, a photocatalytic material g-C3N4-Ti(3+)/TiO2 nanotube arrays was prepared by a facile and viable approach involving a heat treatment followed by an electrochemical reduction step, and it was characterized using instrumental techniques such as X-ray diffraction pattern, Fourier transform-infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy and UV-vis diffuse reflectance spectra. The photocatalytic efficiency of the as-prepared samples towards treating aqueous solution contaminated with phenol was systematically evaluated by a photoelectrocatalytic method and found to be highly dependent on the content of the g-C3N4. At the optimal content of g-C3N4, the apparent photocurrent density of g-C3N4-Ti(3+)/TiO2 was four times higher than that of the pristine TiO2 under visible-light illumination. The enhanced photoelectrocatalytic behavior observed for g-C3N4-Ti(3+)/TiO2 was ascribed to a cumulative impact of both g-C3N4 and Ti(3+), which enhances the photoresponsive behavior of the material into the visible region and facilitates the effective charge separation of photoinduced charge carriers.

IκB kinase ß (IKKß) inhibits p63 isoform γ (TAp63γ) transcriptional activity.

Previously, we reported that IκB kinase-ß(IKKß) phosphorylates and stabilizes TAp63γ. However, the effect of this phosphorylation on TAp63γ transcriptional activity remains unclear. In this study, we showed that overexpression of IKKß, but not its kinase dead mutant and IKKα, can surprisingly inhibit TAp63γ transcriptional activity as measured by luciferase assays and real-time PCR analyses of p63 target genes. This inhibition was impaired by ACHP, an IKKß inhibitor, and enhanced by TNFα that activates IKKß. Consistently, IKKß inhibited the binding between TAp63γ and p300, a co-activator of TAp63γ, and consequently counteracted the positive effect of p300 on TAp63γ transcriptional activity. Through phosphorylation site prediction and mass spectrometry, we identified that Ser-4 and Ser-12 of p63 are IKKß-targeting residues. As expected, IKKß fails to suppress the transcriptional activity of the S4A/S12A double mutant p63. These results indicate that IKKß can suppress TAp63γ activity by interfering with the interaction between TAp63γ and p300.

Human Umbilical Cord Mesenchymal Stem Cells Alleviate Chronic Salpingitis by Modulating Macrophage-Associated Inflammatory Factors.

INTRODUCTION: Mesenchymal stem cells (MSCs) have been widely studied because of their established anti-inflammatory properties. During chronic salpingitis (CS), infiltrated macrophages have vital roles in inflammation and tissue remodeling. METHODS: We employed the type of MSCs, human umbilical cord (huc) MSCs in an experimental CS model and therapeutic efficacy was assessed. hucMSCs exerted this therapeutic effect by regulating macrophage function. To verify the regulatory effects of hucMSCs on the macrophage, macrophage line RAW264.7 markers were analyzed under LPS stimulation with or without co-culturing with hucMSCs for 12h and 24h. In addition, flow cytometry analysis was applied to reveal the interaction of co-culture. For animal studies, CS was induced by the MoPn strain Chlamydia trachomatis (CT), hucMSCs were intravaginally injected in the CS, and we analyzed the infiltrated macrophage by immunofluorescence. RESULTS: We found the markers IL-10 was markedly increased and IL-1ß, caspase-1 was notably downregulated after co-culturing with hucMSCs by RT-PCR. hucMSCs promote macrophage line RAW264.7 apoptosis. We also found that hucMSCs treatment can alleviate CS by decreasing the mRNA expression of IL-1ß, caspase-1 and MCP-1 in the tubal tissue by RT-PCR and decreasing the protein expression of IL-1ß, caspase-1 and TGF-ß by western blotting. CONCLUSION: These results suggest that macrophage function may be related to the immune-modulating characteristics of hucMSCs that contribute to CS.

Fe(II)-catalyzed phase transformation of Cd(II)-bearing ferrihydrite-kaolinite associations under anoxic conditions: New insights to role of kaolinite and fate of Cd(II).

Cadmium-bearing ferrihydrite-kaolinite associations (Cd-associations) are commonly found in cadmium-contaminated paddy soils in tropical and subtropical regions. In the presence of anaerobic conditions caused by flooding, the creation of Fe(II) can facilitate the transformation of ferrihydrite into secondary Fe (hydr)oxides, resulting in the redistribution of Cd. However, the role of kaolinite in iron oxides transformation and changes in Cd chemical species have largely not been determined. In this study, Cd-associations were prepared for reaction with Fe(II) under anoxic conditions. The results obtained from powder XRD and EXAFS indicated that the presence of kaolinite association noticeably hastened the transformation of ferrihydrite into crystalline goethite. Specific surface area and electrochemical analyses revealed that smaller particle sizes and higher reactivity of ferrihydrite within Cd-associations collaboratively contribute to the acceleration. Chemical analyses demonstrated a significant negative correlation between ferrihydrite-Fe and aqueous-Cd, and a significant positive correlation between crystalline-Fe and residual-Cd. HRTEM analyses indicated that a portion of the Cd was incorporated into the crystal lattices of lepidocrocite and goethite, with the majority of Cd being sequestered within goethite lattice. These findings provide new insights into the roles of clay minerals in the geochemical cycling of Fe and Cd in paddy soils under anoxic conditions.

Phytic acid inhibits Cr(VI) reduction on Fe(II)-bearing clay minerals: Changing reduction sites and electron transfer pathways.

The presence of organic phosphorus may influence the characteristics of Cr(VI) reduction and immobilization on Fe(II)-bearing clay minerals under anoxic conditions, as the organic phosphorus tends to bind strongly to clay minerals in soil. Herein, reduced nontronite (rNAu-2) was used to reduction of Cr(VI) in the presence of phytic acid (IHP) at neutral pH. With IHP concentration from 0 to 500 µM, Cr(VI) reduction decreased obviously (17.8%) within first 5 min, and then preferred to stagnate during 4-12 h (≥50 µM). After that, Cr(VI) was reduced continuously at a slightly faster rate. Density functional theory (DFT) calculations revealed that IHP primarily absorbed at the edge sites of rNAu-2 to form Fe-IHP complexes. X-ray diffraction (XRD), scanning transmission electron microscopy (STEM), and Fourier transform infrared spectroscopy (FTIR) results demonstrated that IHP hindered the ingress of CrO42- into the interlayer space of rNAu-2 and impeded their reduction by trioctahedral Fe(II) and Al-Fe(II) at basal plane sites in the initial stage. Additionally, Fe(II) extraction results showed that IHP promoted the electron from interior transfer to near-edge, but hindered it further transfer to surface, resulting in the inhibition on Cr(VI) reduction at edge sites during the later stage. Consequently, IHP inhibits the reduction and immobilization of Cr(VI) by rNAu-2. Our study offers novel insights into electron transfer pathways during the Cr(VI) reduction by rNAu-2 with coexisting IHP, thereby improve the understanding of the geochemical processes of chromium within the iron cycle in soil.

Dramatically enhanced phenol degradation upon FeS oxygenation by low-molecular-weight organic acids.

Oxidizing potential of FeS for organic contaminants degradation due to hydroxyl radicals (•OH) production has been recently documented, but the oxidizing efficiency was limited. Here, we revealed that low-molecular-weight organic acids (LMWOAs) can immensely enhance phenol degradation during FeS oxygenation due to increased utilization efficiency of FeS electron for •OH production. Upon oxygenation of 0.5 g/L FeS, phenol degradation boosted from 7.1% without LMWOAs to 91.5%, 84.6% and 95.0% with the addition of 1 mM oxalate, citrate and EDTA, respectively. Electron utilization efficiency of Fe(II) for •OH production dramatically rose from 0.3% with FeS alone to respective 2.0%, 2.5% and 2.7% in the LMWOAs systems. An increase in oxalate concentrations benefited •OH formation and phenol degradation. Coexisting oxalate led to an additional •OH production pathway from Fe(II)-oxalate oxidation, which expanded the O2 reduction to H2O2 from a two- to one-electron transfer process. Meanwhile, electron transfer from FeS to dissolved Fe(III)-oxalate promoted the redox cycling of Fe(III)/Fe(II), thus supplying the Fe(II) oxidation for •OH production. Moreover, the presence of oxalate decreased the crystallinity and particles size of lepidocrocite generated from FeS oxidation. Consequently, this study shed lights on the LMWOAs-enhanced contaminant degradation in either natural or engineered FeS oxidation systems.

Phenylarsonics in concentrated animal feeding operations: Fate, associated risk, and treatment approaches.

Phenylarsonics are present as additives in animal feed in some countries. As only a small fraction of these additives is metabolized in animals, they mostly end up in the environment. A comprehensive investigation of the fate of these additives is crucial for evaluating their risks. This review aims to provide a clear understanding of the transformation mechanism of phenylarsonics in vivo and in vitro and to evaluate their fate and associated risks. Degradation of phenylarsonics releases toxic As species (mainly as inorganic arsenic (iAs)). Trivalent phenylarsonics are the metabolites or biotic degradation intermediates of phenylarsonics. The cleavage of As groups from trivalent phenylarsonics catalyzed by C-As lyase or other unknown pathways generates arsenite (As(III)). As(III) can be further oxidized to arsenate (As(V)) and methylated to methyl-arsenic species. The half-lives associated with abiotic degradation of phenylarsonics ranged from a few minutes to tens of hours, while those associated with biotic degradation ranged from several days to hundreds of days. Abiotic degradation resulted in a higher yield of iAs than biotic degradation. The use of phenylarsonics led to elevated total As and iAs levels in animal products and environmental matrices, resulting in As exposure risk to humans. The oxidation of phenylarsonics to As(V) facilitated the sorptive removal of As, which provides a general approach for treating these compounds. This review provides solid evidence that the use of phenylarsonics has adverse effects on both human health and environmental safety, and therefore, supports their withdrawal from the global market.

The clinical significance of glutathione peroxidase 2 in glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the leading cause of death among adult brain cancer patients. Glutathione peroxidase 2 (GPX2), as a factor in oxidative stress, plays an important role in carcinogenesis. However, its role in GBM has not been well established. The study aimed to investigate the clinical significance of GPX2 with GBM prognosis. METHODS: Data of GBM and healthy individuals were retrospectively collected from oncomine, cancer cell line encyclopedia (CCLE), gene expression profiling interactive analysis (GEPIA), UALCAN, and Human Protein Atlas. GPX2 mRNA expression was first assessed across various cancer types in oncomine and cancer cell lines from CCLE. The mRNA expression of GPX2 was compared between normal and GBM tissues using GEPIA (normal = 207; GBM = 163) and UALCAN (normal = 5; GBM = 156). The GPX2 methylation was analyzed using data from UALCAN (normal = 2; GBM = 140). The prognostic value of GPX2 in GBM was explored in GEPIA and UALCAN using Kaplan-Meier method. STRING database was used to construct protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Statistical significance was set as <0.05. RESULTS: The current study revealed no significant differences in GPX2 expression between normal and GBM from GEPIA data (P > 0.05) and UALCAN (P = 0.257). Patients with higher GPX2 intended to have a poorer prognosis (P = 0.0089). The KEGG pathways found that chemokine-signaling pathway were the more preferred. CONCLUSIONS: The findings demonstrated that GPX2 might be a potential diagnosis and prognostic indicator for GBM. Chemokine-signaling pathway may be involved in GPX2 function.

Does lineage plasticity enable escape from CAR-T cell therapy? Lessons from MLL-r leukemia.

The clinical success of engineered, CD19-directed chimeric antigen receptor (CAR) T cells in relapsed, refractory B-cell acute lymphoblastic leukemia (B-ALL) has generated great enthusiasm for the use of CAR T cells in patients with cytogenetics that portend a poor prognosis with conventional cytotoxic therapies. One such group includes infants and children with mixed lineage leukemia (MLL1, KMT2A) rearrangements (MLL-r), who fare much worse than patients with low- or standard-risk B-ALL. Although early clinical trials using CD19 CAR T cells for MLL-r B-ALL produced complete remission in most patients, relapse with CD19-negative disease was a common mechanism of treatment failure. Whereas CD19neg relapse has been observed across a broad spectrum of B-ALL patients treated with CD19-directed therapy, patients with MLL-r have manifested the emergence of AML, often clonally related to the B-ALL, suggesting that the inherent heterogeneity or lineage plasticity of MLL-r B-ALL may predispose patients to a myeloid relapse. Understanding the factors that enable and drive myeloid relapse may be important to devise strategies to improve durability of remissions. In this review, we summarize clinical observations to date with MLL-r B-ALL and generally discuss lineage plasticity as a mechanism of escape from immunotherapy.

The comet assay: a sensitive method for detecting DNA damage in individual cells.

The comet assay is a sensitive and rapid method for DNA strand break detection in individual cells, and the year 2009 represents the 25th anniversary of the first description of this methodology in 1984. Over time this method has been improved, but is still not completely standardized, and variations are currently in widespread use with emphasis on applications in research and genetic toxicology. Here we review the principles of the comet assay and cite key studies that have focused on this assay in the past 25 years. In addition, we present an example of how the comet assay was used in our laboratory for studying the induction of DNA damage in human lung cancer cells after differing doses of the cytosine analog 5-aza-2'-deoxycytidine (5-aza-CdR). Finally, some insights into the potential of this assay in cancer research and work in related fields are offered.

Sulfide drives hydroxyl radicals production in oxic ferric oxyhydroxides environments.

Perturbation of Fe(III)-bearing oxic environments by reduced species such as sulfide occurs widely in natural and engineered systems. However, whether hydroxyl radicals (OH) can be produced in these environments remains unexplored. Here we show that sulfide drives OH production in Fe(III) oxyhydroxides suspensions under neutral and oxic conditions. For lepidocrocite, ferrihydrite and goethite suspensions at 11.2 mM Fe, the addition of 0.5 mM sulfide produced 14.2, 14.3 and 22.4 µM OH within 120 min, respectively. With addition of sulfide to lepidocrocite suspensions at 11.2 mM Fe, the cumulative OH concentration within 120 min increased from 0 to 14.2, 25.2, 52.6 and 63.1 µM when sulfide dosage increased from 0 to 0.5, 2.5, 5 and 7.5 mM, respectively. At a fixed sulfide dosage of 5 mM, the cumulative OH concentration increased with increasing the number of sulfide additions. The mechanisms of OH production were attributed to the generation of surface-bound Fe(II), most likely in the form of >FeIIOH2+, and Fe(II) in the solid phase or FeS from the reactions between sulfide and Fe(III), followed by O2 activation. OH production could take place until depletion of sulfide. Finally, we found that the generated OH could oxidize the coexisting redox-active substances like phenol under neutral and oxic conditions. Our findings reveal that sulfide perturbation of Fe(III)-bearing oxic environments is a new source of OH, and contaminants oxidation by OH necessitates consideration in these environments.