Storage and Distribution of Organic Carbon and Nutrients in Acidic Soils Developed on Sulfidic Sediments: The Roles of Reactive Iron and Macropores.

In a boreal acidic sulfate-rich subsoil (pH 3-4) developing on sulfidic and organic-rich sediments over the past 70 years, extensive brownish-to-yellowish layers have formed on macropores. Our data reveal that these layers ("macropore surfaces") are strongly enriched in 1 M HCl-extractable reactive iron (2-7% dry weight), largely bound to schwertmannite and 2-line ferrihydrite. These reactive iron phases trap large pools of labile organic matter (OM) and HCl-extractable phosphorus, possibly derived from the cultivated layer. Within soil aggregates, the OM is of a different nature from that on the macropore surfaces but similar to that in the underlying sulfidic sediments (C-horizon). This provides evidence that the sedimentary OM in the bulk subsoil has been largely preserved without significant decomposition and/or fractionation, likely due to physiochemical stabilization by the reactive iron phases that also existed abundantly within the aggregates. These findings not only highlight the important yet underappreciated roles of iron oxyhydroxysulfates in OM/nutrient storage and distribution in acidic sulfate-rich and other similar environments but also suggest that boreal acidic sulfate-rich subsoils and other similar soil systems (existing widely on coastal plains worldwide and being increasingly formed in thawing permafrost) may act as global sinks for OM and nutrients in the short run.

A novel Mcl-1 inhibitor synergizes with venetoclax to induce apoptosis in cancer cells.

BACKGROUND: Evading apoptosis by overexpression of anti-apoptotic Bcl-2 family proteins is a hallmark of cancer cells and the Bcl-2 selective inhibitor venetoclax is widely used in the treatment of hematologic malignancies. Mcl-1, another anti-apoptotic Bcl-2 family member, is recognized as the primary cause of resistance to venetoclax treatment. However, there is currently no Mcl-1 inhibitor approved for clinical use. METHODS: Paired parental and Mcl-1 knockout H1299 cells were used to screen and identify a small molecule named MI-238. Immunoprecipitation (IP) and flow cytometry assay were performed to analyze the activation of pro-apoptotic protein Bak. Annexin V staining and western blot analysis of cleaved caspase 3 were employed to measure the cell apoptosis. Mouse xenograft AML model using luciferase-expressing Molm13 cells was employed to evaluate in vivo therapeutic efficacy. Bone marrow samples from newly diagnosed AML patients were collected to evaluate the therapeutic potency. RESULTS: Here, we show that MI-238, a novel and specific Mcl-1 inhibitor, can disrupt the association of Mcl-1 with BH3-only pro-apoptotic proteins, selectively leading to apoptosis in Mcl-1 proficient cells. Moreover, MI-238 treatment also potently induces apoptosis in acute myeloid leukemia (AML) cells. Notably, the combined treatment of MI-238 with venetoclax exhibited strong synergistic anti-cancer effects in AML cells in vitro, MOLM-13 xenografts mouse model and AML patient samples. CONCLUSIONS: This study identified a novel and selective Mcl-1 inhibitor MI-238 and demonstrated that the development of MI-238 provides a novel strategy to improve the outcome of venetoclax therapy in AML.

Mobility and environmental impact of cadmium (Cd) during weathering of carbonaceous black shales in western Hunan, China.

Carbonaceous black shale generally contains high concentration of Cd, with weathering leading to Cd release to environment. In this study, the mobility of Cd during weathering was quantified using geochemical assessment on black shale from western Hunan, China. Results suggested that Cd was heterogeneously distributed in shale profiles with concentrations ranging from 0.16 to 109.9 (mg/kg). Cd distribution was heterogeneous resulting from the parent shale inheritance and the mobility of Cd during weathering. Black shales weathered to a moderate degree with Cd mobility characterized by both enrichment in and release from weathered shales. Cd enrichment in weathered shales resulted from the re-enrichment of Cd in secondary minerals formed during the initial stage of carbonate (and phosphorite) dissolution, and the secondary stage of sulfide oxidation. The release of Cd was caused by decomposition of the secondary Cd-bearing minerals. Cadmium was extensively released during pedogenesis, and Cd release mass flux was estimated to range from 1.26 to 9.50 (g/m2) with a mean of 6.60 g/m2. Thus, black shale weathering may lead to the releasing of large amount of Cd resulting in Cd contamination to local environments.

Distribution, source and contamination of rare earth elements in sediments from lower reaches of the Xiangjiang River, China.

Rare earth elements (REEs) are emerging micropollutants in aquatic environments. In this study, concentrations of REEs and major elements, and mineralogical compositions of sediments from lower reaches of the Xiangjiang River (China) were analyzed using ICP-MS technique. The results suggested that sediments were characterized by terrigenous compositions TiO2, SiO2, Al2O3, K2O, Na2O and P2O, and contained high concentrations of REEs with mean total REE concentrations (∑REE) of 318.7 mg/kg. REEs were moderately enriched in upper river sediments, and slightly or less enriched in downriver sediments. The normalized REE distribution pattern for sediments was characterized by flat shalelike and Eu depleted V-shape REE patterns, which indicated REEs in sediments were lithologically contributed from sedimentary rocks and granites distributed in the watershed respectively. REEs in sediments were hosted mainly in Fe-Mn oxides, and sulfide and organic matters that were characterized by middle REEs (MREE) enrichments relative to light REEs (LREE) and heavy REEs (HREE), and the distribution and differentiation of REEs in sediments were controlled by clays, Fe-Mn oxides, organic matters and finer grains; and also by accessory minerals (e.g., zircon) from granite. The distribution features of REEs in sediments and BCR extraction results suggested that the sediment REE enrichment resulted from additional REE input from anthropogenic sources, including those in discharges from sulfide-ore smelting industries at Zhuzhou city and from phosphate fertilizer plants at Xiangtan city along the river. Thus, sediments were contaminated with REEs in moderate degree in upper river area, and REE contamination was then formed by superimposing anthropogenic REEs on lithological residues. Finally, concentrations of Ce > 100 mg/kg, Gd > 8.12 mg/kg, ∑REE >274.9 mg/kg, ∑LREE >252.3 mg/kg and ∑HREE >28.8 mg/kg here were recommended as the REE contamination levels that represented as REE indices for identifying and rating REE contamination in this mining impacted river.

Effect of weathering on abundance and release of potentially toxic elements in soils developed on Lower Cambrian black shales, P. R. China.

This paper examines the geochemical features of 8 soil profiles developed on metalliferous black shales distributed in the central parts of the South China black shale horizon. The concentrations of 21 trace elements and 8 major elements were determined using ICP-MS and XRF, respectively, and weathering intensity (W) was calculated according to a new technique recently proposed in the literature. The data showed that the black shale soils inherited a heterogeneous geochemical character from their parent materials. A partial least square regression model and EF(bedrock) (enrichment factor normalized to underlying bedrock) indicated that W was not a major control in the redistribution of trace metals. Barium, Sn, Cu, V, and U tended to be leached in the upper soil horizons and trapped by Al and Fe oxides, whereas Sb, Cd, and Mo with negative EF values across the whole profiles may have been leached out during the first stage of pedogenesis (mainly weathering of black shale). Compared with the Chinese average soils, the soils were strongly enriched in the potentially toxic metals Mo, Cd, Sb, Sn, U, V, Cu, and Ba, among which the 5 first listed were enriched to the highest degrees. Elevated concentrations of these toxic metals can have a long-term negative effect on human health, in particular, the soils in mining areas dominated by strongly acidic conditions. As a whole, the black shale soils have much in common with acid sulfate soils. Therefore, black shale soils together with acid sulfate soils deserve more attention in the context of metal exposure and human health.

Distribution of Pb isotopes in different chemical fractions in bed sediments from lower reaches of the Xiangjiang River, Hunan province of China.

This paper reports Pb isotopes in different fractions following the three step BCR and 1 M HCl extractions on river sediments from lower reaches of the Xiangjiang river in China, and highlights the importance of Pb isotopes in heavy metal contamination assessment. Lead concentrations and Pb isotopes in bulk sediments and sediment fractions (leachates and residues) from the river were analysed using ICP-MS techniques. Results showed that sediments were highly enriched with Pb with enrichment factors >5.5, while Pb in sediments was dominated by reducible and residual Pb fractions, residing mainly in Fe-oxide and silicate minerals. Pb isotopes in sediments was characterized by radiogenic Pb produced from the decay of uranium and thorium with 206Pb/207Pb ratios of 1.1744 for less radiogenic Pb and 1.1816 for more radiogenic Pb. The leachates and residues from BCR extraction generally had similar Pb isotope compositions, of which the 206Pb/207Pb ratios were 1.1798 ± 0.002 and 1.1844 ± 0.008 respectively. Differentiation of Pb isotopes between BCR leachates and residues was insignificant. However, differentiation between leachates and residues using 1 M HCl extraction was significant, as shown by average 206Pb/207Pb ratios of 1.1746 ± 0.005 and 1.1858 ± 0.008 for leachates and residues respectively. Pb isotopic tracing suggests that Pb in sediments from Zhuzhou section arose from the mixing of anthropogenic Pb from coal combustion (39%) and mining-smelting for Pb-Zn ores (58%); while Pb in sediments from Xiangtan, Changsha and Xiangyin sections arose from the mixing of anthropogenic Pb from mining-smelting for Pb-Zn ores (54%), and lithologically inherited Pb from granite weathering (35%) with a small amount of contribution from coal combustion (10%). The present study suggests that the BCR extraction scheme was not appropriate for ecological risk assessment of heavy metal contamination in mining-impacted (ore-Pb dominated) river sediments.

Distribution and assessment of cadmium contamination in sediments from the Four River inlets to Dongting Lake, China.

The total concentrations of Cd in bulk sediments and those of the BCR sequential extraction fractions of sediments from inlets of the Four Rivers that feed Dongting Lake were determined using ICP-MS techniques. The results suggested that Cd was heterogeneously distributed in the inlet sediments of the rivers, with the highest degree of enrichment in sediments from the Xiangjiang River. The Cd anomaly was defined as Cd enrichment in sediments with an EF (enrichment factor) > 10.0, and it was identified in the inlet sediments of the Xiangjiang River. Cd in the sediments was dominated by acid-soluble Cd at a proportion of 23.9-69.8 (%) compared to its total concentrations in the sediments. The inlet sediments of the Four Rivers were contaminated with Cd, with the highest degree of contamination in the inlet sediments of the Xiangjiang River. The Cd contamination as well as the Cd anomaly in the sediments were closely related to the industrial activities (e.g. smelting and refining for ore minerals) in the areas, and Cd contamination at high levels may represent an ecological risk for the lake watershed. Cd contamination of the inlet sediments may also impact the lake basin sediments and is harmful to the lake ecological system, particularly for sediments of the Xiangjiang River. Therefore, it is essential to control and treat Cd contamination in the inlet sediments for ecological environmental protection of lake watersheds.

A Novel miRNA Restores the Chemosensitivity of AML Cells Through Targeting FosB.

The heterogeneous nature of acute myeloid leukemia (AML) and its poor prognosis necessitate therapeutic improvement. Current advances in AML research yield important insights regarding both AML genetics and epigenetics. MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation, and survival and may be useful for AML diagnosis and prognosis. In this study, a novel miRNA, hsa-miR-12462, was identified in bone marrow (BM) samples from AML patients at diagnosis by small RNA sequencing. A significant higher level of hsa-miR-12462 was found in patients who achieve complete remission (AML-CR) after induction therapy compared with those who suffer relapse/refractory (AML-RR). FosB was predicted to be the target of hsa-miR-12462 through RNA sequencing, bioinformatics analysis, and protein-protein interaction (PPI) network analysis and then verified by luciferase activity assay. T-5224, the inhibitor of FosB, was administered to AML cell lines, which could inhibit cell proliferation, promote apoptosis, and restore the sensitivity of AML cells to cytarabine (Ara-C). In summary, a higher level of hsa-miR-12462 in AML cells is associated with increased sensitivity to Ara-C via targeting FosB.

[Contrast study on natural radioactive nuclides contents of rice between Xiangshan uranium deposit area, Jiangxi and non-uranium depsoit area].

The contents of natural radioactive nuclides such as uranium and thorium in paddies were analyzed and compared by means of ICP-MS. Totally 14 paddy samples were distinguished into two groups and collected from two rice planting area. One group (12 paddy samples) was collected from the Xiangshan uranium deposit area, Jiangxi province; while the other group (2 samples) collected from non-uranium deposit suburban area of Fuzhou city, Jiangxi, as comparison samples. The distance between the two sampling areas is about 80 kilometers. Before analysis, those paddy samples were continuously carbonized by two hours first, then continuously incinerated for 8 hours at the temperature of 600 degrees centigrade. The results show that the uranium contents in the paddy ash of samples gotten from Xiangshan uranium deposit area range from 0.053 to 1.482 microg x g(-1). The uranium contents of two comparison paddy samples ash are 0.059 and 0.061 microg x g(-1), respectiovely. The average uranium content of paddy ash of uranium deposit area is 0.323 microg x g(-1). Compared with the comparison samples, the uranium contents of paddy ash of uranium deposit area are considerably high, 5.30 times that of non-uranium deposit area. The thorium contents in paddy ash of the uranium deposit area, however, are relatively low and less than that of samples collected from non-uranium deposit area, which range from 0.029 to 0.311 microg x g(-1); The average level is 0.104 microg x g(-1), only about 50% of that of paddy ash sampled from non-urnaium deposit area. Moreover, there is significant linearity correlation between uranium and thorium contents of paddy sampled from Xiangshan uranium deposit area. The positive effects show that the thorium contents of paddy increase as uranium contents of paddy in uranium deposit area increase. The causes for the remarkable difference in uranium contents in paddy between urianium deposit area and non-uranium deposit area are not clear yet. The research on this topic, however, is very important and significant to the regional rice quality and food security.