Contaminant migration and the retention behavior of a laterite-bentonite mixture engineered barrier in a landfill.

Groundwater pollution has become increasingly severe in recent years, particularly owing to leachate leakage in landfills. In this study, the migration of Cu2+ in a landfill and the retention behavior of a compacted laterite-bentonite engineered barrier system toward the contaminant were analyzed by a numerical simulation based on laboratory and field test results. The results show that the hydraulic conductivity of the laterite-bentonite mixture decreased with an increase in the bentonite ratio: The hydraulic conductivities of the laterite-bentonite mixture were 4.718 × 10-7, 2.103 × 10-7, 7.899 × 10-8, 3.918 × 10-8, and 1.614 × 10-8 cm/s when the bentonite ratios were 0, 2%, 5%, 10%, and 20%, respectively. The hydraulic conductivity of laterite and of the mixture with a bentonite ratio of 2% decreased gradually under infiltration of deionized water and CuSO4 solutions with concentrations of 0.01 and 0.1 mol/L. This could be attributed to the increased degree of flocculation of laterite with the increase in the solution concentration. The results of the numerical simulation indicate that the migration range of Cu2+ after 3650 days was approximately 1500 m. The retention efficiency of a 0.5 m engineered barrier for Cu2+ was 67%. However, the retention efficiency exceeded 83% when the engineered barrier thickness was increased to 1.0 m. The results of the laboratory tests and numerical simulation demonstrate that a compacted laterite-bentonite engineered barrier system has a good retention effect on Cu2+. These observations may provide effective concepts for the prevention and control of groundwater pollution in landfills.

The Impact of the Epigenetic Cancer Drug Azacitidine on Host Immunity: The Role of Myelosuppression, Iron Overload and tp53 Mutations in a Zebrafish Model.

The unsatisfactory real-world efficacy of the hypomethylating agent azacitidine in treating myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) has prompted us to investigate the hematological adverse events and host variables that may compromise the use of this epigenetic drug. Using the zebrafish, we found that azacitidine destroyed their myeloid precursors and impaired myeloid function by inhibiting antigen processing, allogeneic response and phagocytic activity, resulting in increased susceptibility to infection even by the normal flora E. coli. In addition, iron overload, a MDS-associated condition following repeated transfusions, exacerbated bacterial infection especially by V. vulnificus with known iron dependence. Furthermore, we show that the tp53M214K mutant zebrafish survived longer than the wild-type (WT) when challenged with bacteria following azacitidine treatment. This was attributed to the mutant's hematopoietic cells rather than its general genetic background, since the WT animals reconstituted with the tp53M214K mutant kidney marrow became more resistant to bacterial infection following treatment with azacitidine. The clinical relevance of our findings was indicated by a MDS case with severe azacitidine-induced bone marrow suppression and by the association of hyperferritinemia with bacteremia in azacitidine-treated patients, while tp53M214K-mediated resistance to azacitidine-induced myelosuppression may explain the survival advantage of malignant MDS and AML clones over their normal counterparts under azacitidine treatment. Together, we propose that myelosuppression, iron overload and TP53 mutations may represent the host variables that compromise the azacitidine efficacy.

Bortezomib-induced miRNAs direct epigenetic silencing of locus genes and trigger apoptosis in leukemia.

MicroRNAs (miRNAs) have been suggested to repress transcription via binding the 3'-untranslated regions of mRNAs. However, the involvement and details of miRNA-mediated epigenetic regulation, particularly in targeting genomic DNA and mediating epigenetic regulation, remain largely uninvestigated. In the present study, transcription factor CCAAT/enhancer binding protein delta (CEBPD) was responsive to the anticancer drug bortezomib, a clinical and highly selective drug for leukemia treatment, and contributed to bortezomib-induced cell death. Interestingly, following the identification of CEBPD-induced miRNAs, we found that miR-744, miR-3154 and miR-3162 could target CpG islands in the 5'-flanking region of the CEBPD gene. We previously demonstrated that the Yin Yang 1 (YY1)/polycomb group (PcG) protein/DNA methyltransferase (DNMT) complex is important for CCAAT/enhancer binding protein delta (CEBPD) gene inactivation; we further found that Argonaute 2 (Ago2) interacts with YY1 and binds to the CEBPD promoter. The miRNA/Ago2/YY1/PcG group protein/DNMT complex linked the inactivation of CEBPD and genes adjacent to its 5'-flanking region, including protein kinase DNA-activated catalytic polypeptide (PRKDC), minichromosome maintenance-deficient 4 (MCM4) and ubiquitin-conjugating enzyme E2 variant 2 (UBE2V2), upon bortezomib treatment. Moreover, we revealed that miRNA binding is necessary for YY1/PcG group protein/DNMT complex-mediated epigenetic gene silencing and is associated with bortezomib-induced methylation on genomic DNA. The present study successfully characterized the interactions of the miRNA/Ago2/YY1/PcG group protein/DNMT complex and provided new insights for miRNA-mediated epigenetic regulation in bortezomib-induced leukemic cell arrest and cell death.

Measuring interconnection of the residual cortical functional islands in persistent vegetative state and minimal conscious state with EEG nonlinear analysis.

OBJECTIVES: The aim of the study is to investigate the cortical response to painful and auditory stimuli for subjects in persistent vegetative state (PVS) and minimal conscious state (MCS), and measure the interconnection of the residual cortical functional islands with electroencephalographic (EEG) nonlinear dynamic analysis (NDA). METHODS: Thirty PVS subjects, 20 MCS subjects and 30 subjects in normal conscious state (NCS) were involved in the study. EEG was recorded under three conditions: eyes closed, auditory stimuli and painful stimuli. EEG nonlinear index of cross-approximate entropy (C-ApEn) was calculated for all subjects. RESULTS: Interconnection of local and distant cortical networks of patients in PVS was generally suppressed, and painful or auditory stimulation could hardly cause any activation of associative cortices. Instead, interconnection of local cortical networks of patients in MCS improved significantly. The only significant difference with the NCS existed in the unaffected distant cortical networks. CONCLUSIONS: Interconnection of local and distant cortical networks in MCS is superior to that of PVS. NDA could measure interconnection of the residual cortical functional islands with associative cortices in the unconscious patients. SIGNIFICANCE: NDA can characterise the interconnection of cortical networks for the unconscious state and provide some information of unconsciousness at the awareness level.

Application of nonlinear dynamics analysis in assessing unconsciousness: a preliminary study.

OBJECTIVES: To quantify the degree of unconsciousness with EEG nonlinear analysis and investigate the change of EEG nonlinear properties under different conditions. METHODS: Twenty-one subjects in persistent vegetative state (PVS), 16 in minimally conscious state (MCS) and 30 normal conscious subjects (control group) with brain trauma or stroke were involved in the study. EEG was recorded under three conditions: eyes closed, auditory stimuli and painful stimuli. EEG nonlinear indices such as Lempel-Ziv complexity (LZC), approximate entropy (ApEn) and cross-approximate entropy (cross-ApEn) were calculated for all the subjects. RESULTS: The PVS subjects had the lowest nonlinear indices followed by the MCS subjects and the control group had the highest. The PVS and MCS group had poorer response to auditory and painful stimuli than the control group. Under painful stimuli, nonlinear indices of subjects who recovered (REC) increased more significantly than non-REC subjects. CONCLUSIONS: With EEG nonlinear analysis, the degree of suppression for PVS and MCS could be quantified. The changes of brain function for unconscious subjects could be captured by EEG nonlinear analysis. SIGNIFICANCE: EEG nonlinear analysis could characterise the changes of brain function for unconscious state and might have some value in predicting prognosis of unconscious subjects.