ZmASR1 negatively regulates drought stress tolerance in maize.

Abscisic acid-, stress-, and ripening-induced (ASR) proteins in plants play a significant role in plant response to diverse abiotic stresses. However, the functions of ASR genes in maize remain unclear. In the present study, we identified a novel drought-induced ASR gene in maize (ZmASR1) and functionally characterized its role in mediating drought tolerance. The transcription of ZmASR1 was upregulated under drought stress and abscisic acid (ABA) treatment, and the ZmASR1 protein was observed to exhibit nuclear and cytoplasmic localization. Moreover, ZmASR1 knockout lines generated with the CRISPR-Cas9 system showed lower ROS accumulation, higher ABA content, and a higher degree of stomatal closure than wild-type plants, leading to higher drought tolerance. Transcriptome sequencing data indicated that the significantly differentially expressed genes in the drought treatment group were mainly enriched in ABA signal transduction, antioxidant defense, and photosynthetic pathway. Taken together, the findings suggest that ZmASR1 negatively regulates drought tolerance and represents a candidate gene for genetic manipulation of drought resistance in maize.

Environmental impact assessment of acidic coal gangue leaching solution on groundwater: a coal gangue pile in Shanxi, China.

With the continual advancement of coal resource development, the comprehensive utilization of coal gangue as a by-product encounters certain constraints. A substantial amount of untreated coal gangue is openly stored, particularly acidic gangue exposed to rainfall. The leaching effect of acidic solutions, containing heavy metal ions and other pollutants, results in environmental challenges such as local soil or groundwater pollution, presenting a significant concern in the current ecological landscape of mining areas. Investigating the migration patterns of pollutants in the soil-groundwater system and elucidating the characteristics of polluted solute migration are imperative. To understand the migration dynamics of pollutants and unveil the features of solute migration, this study focuses on a coal gangue dump in a mining area in Shanxi. Utilizing indoor leaching experiments and soil column migration experiments, a two-dimensional soil-groundwater model is established using the finite element method of COMSOL. This model quantitatively delineates the migration patterns of key pollutant components leached from coal gangue into the groundwater. The findings reveal that sulfate ions can migrate and infiltrate groundwater within a mere 7 years in the vadose zone of aeration. Moreover, the average concentration of iron ions in groundwater can reach approximately 58.3 mg/L. Convection, hydrodynamic dispersion, and adsorption emerge as the primary factors influencing pollution transport. Understanding the leaching patterns and environmental impacts of major pollutants in acidic coal gangue is crucial for predicting soil-groundwater pollution and implementing effective protective measures.

Guideline for the evaluation of prescription appropriateness.

Evaluation of prescriptions is a necessary process of evaluating the appropriateness of clinical drug usage, discovering existing problems, and formulating solutions. There are challenges for professionals within hospital medical departments and for clinicians and pharmacists who have clinical questions relating to inappropriate or abnormal prescriptions as identified by the electronic evaluation system of prescription. Medications are usually used correctly according to the drug instructions or guidelines. At present, there are no relevant domestic or international guidelines, or principles or standards for identifying inappropriate or abnormal prescriptions. To develop the guideline for evaluation of prescriptions appropriateness in clinical practice, the Pharmaceutical Affairs Commission of the Chinese Hospital Association formed the guideline working group consisting of multidisciplinary experts. The guideline working group summarized clinical questions in the evaluation of prescriptions, searched for supporting evidence, and reached a consensus for recommendations. The guideline contains 6 recommendations for evaluating prescription appropriateness, and the general principle of these recommendations is that clinicians should provide drug instructions, guidelines, or moderate evidence supporting the prescription, and the evaluators will then judge the prescription to be either appropriate or irrational. The recommendations resolve common clinical questions, using supporting examples, explanations and a flow chart. The evaluation of prescription appropriateness could be made more systematic and transparent based on this guideline's conclusions.

Synthesis of submicron spherical Fe-MCM-48 with actual gyroid like structure.

Highly ordered submicron spherical Fe-MCM-48 was successfully synthesized by a mixed surfactant method using cheap water glass as silica source. The gyroid like structure of MCM-48 was captured by a TEM image for the first time, and it was corresponded well to the previous simulated gyroid model. A tentative mechanism of homogenization cooperative process involving the Helmholtz double electrical layer was purposed. After the loading of metal Ag, the resulting Ag/Fe-MCM-48 catalyst showed good catalytic performance in the catalytic combustion of benzene.

t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL.

The most frequent MLL-gene rearrangement found in leukemia is a reciprocal translocation with AF4 on chromosome 4 resulting in the formation of the MLL-AF4 and the AF4-MLL fusion genes. The oncogenic role of MLL-AF4 is documented but the significance of the reciprocal product - AF4-MLL in leukemia is less clear. In the human leukemia cell lines - RS4;11 and SEMK2-M1, both of which express MLL-AF4 and AF4-MLL, we knocked down the expression of AF4-MLL using siRNA. Loss of AF4-MLL had no effect on the growth of either RS4;11 or SEMK2-M1 cells. Furthermore, in SEMK2-M1 cells there were no changes in cell cycle or apoptosis with loss of AF4-MLL. In contrast, knockdown of MLL-AF4 significantly inhibited growth of both RS4;11 and SEMK2-M1. Additionally, in SEMK2-M1 cells, loss of MLL-AF4 led to G2/M cell cycle arrest and increased apoptosis. Overall, these results demonstrate that in t(4;11) leukemia, the MLL-AF4 fusion protein is critical for leukemia cell proliferation and survival while the AF4-MLL fusion product is dispensable.

Preparation of zeolite ANA crystal from zeolite Y by in situ solid phase iso-structure transformation.

A new method has been explored to synthesize zeolite ANA crystals with regular icositetrahedron in aqueous media via transformation of zeolite Y under the conditions of low temperature, short reaction time, and without organic template. The products are perfect, almost 100% crystals. The samples prepared at different crystallization stages are measured by XRD, TEM, and SEM to investigate the transformation mechanism from zeolite Y to zeolite ANA. It has been demonstrated for the first time that the mechanism of forming a zeolite ANA polycrystal with sphere or shell morphologies is the in situ solid phase iso-structure transformation (Is-SPIST) of zeolite Y. The Is-SPIST mechanism is also supported by the results of steam-induced crystallization experiments and other assistant means, including the same Si/Al ratio, the same weight, the same particle size, and the same morphology before and after transformation of zeolite Y to zeolite ANA. It is also observed that a spherical or shell ANA polycrystal is constructed via the reconstruction from its exterior to interior, to form an ANA single crystal with a solid or hollow icositetrahedron. The main driving force of the reconstruction is considered to be the grain boundary energy existing between polycrystalline grains. This process also obeys the mechanism of in situ solid phase reconstruction (Is-SPR). Furthermore, the size and morphology of the zeolite ANA single crystal can be modified by surfactants.

Synthesis of high quality MCM-48 with binary cationic-nonionic surfactants.

Highly ordered MCM-48 was synthesized in the hydrothermal system of a mixture of cationic cetyltrimethylammonium bromide (CTAB) and nonionic poly(ethylene glycol) monooctylphenyl ether (Tx-100) using water glass as the silicon source. The effect of various factors, such as the amount of surfactant, CTAB/Tx-100, Si source, crystallization temperature, and crystallization time, on the synthesis were discussed in detail. The local effective surfactant packing parameter theory and the charge balance theory were used to explain the reason that various factors can affect the product structure reasonably. Especially, the role of Tx-100 was expounded. The optimum synthesis conditions for MCM-48 were obtained.

A role for MEIS1 in MLL-fusion gene leukemia.

Leukemias with MLL rearrangements are characterized by high expression of the homeobox gene MEIS1. In these studies, we knocked down Meis1 expression by shRNA lentivirus transduction in murine Mll-AF9 leukemia cells. Meis1 knockdown resulted in decreased proliferation and survival of murine Mll-AF9 leukemia cells. We also observed reduced clonogenic capacity and increased monocytic differentiation. The establishment of leukemia in transplantation recipients was significantly delayed by Meis1 knockdown. Gene expression profiling of cells transduced with Meis1 shRNA showed reduced expression of genes associated with cell cycle entry and progression. shRNA-mediated knockdown of MEIS1 in human MLL-fusion gene leukemia cell lines resulted in reduced cell growth. These results show that MEIS1 expression is important for MLL-rearranged leukemias and suggest that MEIS1 promotes cell-cycle entry. Targeting MEIS1 may have therapeutic potential for treating leukemias expressing this transcription factor.

Malignant transformation initiated by Mll-AF9: gene dosage and critical target cells.

The pathways by which oncogenes, such as MLL-AF9, initiate transformation and leukemia in humans and mice are incompletely defined. In a study of target cells and oncogene dosage, we found that Mll-AF9, when under endogenous regulatory control, efficiently transformed LSK (Lin(-)Sca1(+)c-kit(+)) stem cells, while committed granulocyte-monocyte progenitors (GMPs) were transformation resistant and did not cause leukemia. Mll-AF9 was expressed at higher levels in hematopoietic stem (HSC) than GMP cells. Mll-AF9 gene dosage effects were directly shown in experiments where GMPs were efficiently transformed by the high dosage of Mll-AF9 resulting from retroviral transduction. Mll-AF9 upregulated expression of 192 genes in both LSK and progenitor cells, but to higher levels in LSKs than in committed myeloid progenitors.

Identifying important concepts from medical documents.

Automated medical concept recognition is important for medical informatics such as medical document retrieval and text mining research. In this paper, we present a software tool called keyphrase identification program (KIP) for identifying topical concepts from medical documents. KIP combines two functions: noun phrase extraction and keyphrase identification. The former automatically extracts noun phrases from medical literature as keyphrase candidates. The latter assigns weights to extracted noun phrases for a medical document based on how important they are to that document and how domain specific they are in the medical domain. The experimental results show that our noun phrase extractor is effective in identifying noun phrases from medical documents, so is the keyphrase extractor in identifying important medical conceptual terms. They both performed better than the systems they were compared to.

A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy.

The 2 most frequent human MLL hematopoietic malignancies involve either AF4 or AF9 as fusion partners; each has distinct biology but the role of the fusion partner is not clear. We produced Mll-AF4 knock-in (KI) mice by homologous recombination in embryonic stem cells and compared them with Mll-AF9 KI mice. Young Mll-AF4 mice had lymphoid and myeloid deregulation manifest by increased lymphoid and myeloid cells in hematopoietic organs. In vitro, bone marrow cells from young mice formed unique mixed pro-B lymphoid (B220(+)CD19(+)CD43(+)sIgM(-), PAX5(+), TdT(+), IgH rearranged)/myeloid (CD11b/Mac1(+), c-fms(+), lysozyme(+)) colonies when grown in IL-7- and Flt3 ligand-containing media. Mixed lymphoid/myeloid hyperplasia and hematologic malignancies (most frequently B-cell lymphomas) developed in Mll-AF4 mice after prolonged latency; long latency to malignancy indicates that Mll-AF4-induced lymphoid/myeloid deregulation alone is insufficient to produce malignancy. In contrast, young Mll-AF9 mice had predominately myeloid deregulation in vivo and in vitro and developed myeloid malignancies. The early onset of distinct mixed lymphoid/myeloid lineage deregulation in Mll-AF4 mice shows evidence for both "instructive" and "noninstructive" roles for AF4 and AF9 as partners in MLL fusion genes. The molecular basis for "instruction" and secondary cooperating mutations can now be studied in our Mll-AF4 model.

FLT3 expressing leukemias are selectively sensitive to inhibitors of the molecular chaperone heat shock protein 90 through destabilization of signal transduction-associated kinases.

PURPOSE: We conducted studies to evaluate the hypothesis that FLT3 is a client of heat shock protein (Hsp) 90 and inhibitors of Hsp90 may be useful for therapy of leukemia. EXPERIMENTAL DESIGN: The effects of the Hsp90-inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) on cell growth, expression of signal transduction kinases, apoptosis, FLT3 phosphorylation and interaction with Hsp90 was determined in FLT3(+) human leukemias. RESULTS: We found that FLT3 is included in a multiprotein complex that includes Hsp90 and p23. 17-AAG inhibited FLT3 phosphorylation and interaction with Hsp90. FLT3(+) leukemias were significantly more sensitive to the Hsp90 inhibitors 17-AAG and Herbimycin A in cell growth assays than FLT3-negative leukemias. Cells transfected with FLT3 became sensitive to 17-AAG. Cell cycle inhibition and apoptosis were induced by 17-AAG. Cells with constitutive expression of FLT3, as a result of internal tandem duplication, were the most sensitive; cells with wild-type FLT3 were intermediate in sensitivity, and FLT3-negative cells were the least sensitive. 17-AAG resulted in reduced cellular mass of FLT3, RAF, and AKT. The mass of another Hsp, Hsp70, was increased. The expression level of MLL-AF4 fusion protein was not reduced by 17-AAG in human leukemia cells. CONCLUSIONS: FLT3(+) leukemias are sensitive to 17-AAG and Herbimycin A. 17-AAG inhibits leukemia cells with either FLT3-internal tandem duplication or wild-type FLT3, in part through destabilization of client kinases including FLT3, RAF, and AKT. 17-AAG is potentially useful for therapy of FLT3-expressing leukemias, including the mixed lineage leukemia fusion gene leukemias.