Unmasking Spatial Heterogeneity in Phytotoxicology Mechanisms Induced by Carbamazepine by Mass Spectrometry Imaging and Multiomics Analyses.

Previous studies have highlighted the toxicity of pharmaceuticals and personal care products (PPCPs) in plants, yet understanding their spatial distribution within plant tissues and specific toxic effects remains limited. This study investigates the spatial-specific toxic effects of carbamazepine (CBZ), a prevalent PPCP, in plants. Utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), CBZ and its transformation products were observed predominantly at the leaf edges, with 2.3-fold higher concentrations than inner regions, which was confirmed by LC-MS. Transcriptomic and metabolic analyses revealed significant differences in gene expression and metabolite levels between the inner and outer leaf regions, emphasizing the spatial location's role in CBZ response. Notably, photosynthesis-related genes were markedly downregulated, and photosynthetic efficiency was reduced at leaf edges. Additionally, elevated oxidative stress at leaf edges was indicated by higher antioxidant enzyme activity, cell membrane impairment, and increased free fatty acids. Given the increased oxidative stress at the leaf margins, the study suggests using in situ Raman spectroscopy for early detection of CBZ-induced damage by monitoring reactive oxygen species levels. These findings provide crucial insights into the spatial toxicological mechanisms of CBZ in plants, forming a basis for future spatial toxicology research of PPCPs.

Characteristics of dissolved organic matter during the cyanobacterial degradation in Chaohu Lake, China.

The actual DOM in Chaohu Lake was used to feed cyanobacterial to explore the changes of microbial communities, fluorescence spectral characteristics and molecular composition of DOM during the degradation of cyanobacteria. It is found that cyanobacterial grow periodically depending on the concentration of nutrients with the decreasing concentration of nutrient salts. Both Bacteroidetes and Actinobacteria have strong correlation with algae growth. Bacteroidetes has a positive correlation with algae growth, relationship on the contrary, Actinobacteria has a negative relationship. The humus-like components in the four groups are similar, but the protein-like component (C3) shows periodic changes with the life process of cyanobacteria. The average molecular weight of each sample detected by Orbitrap high-resolution mass spectrometer increases slightly and the DOM increase aromaticity in the end. In this study, the molecule of Carboxyl-Rich Alicyclic Molecules (CRAM) is difficult to be done by photodegradation and biodegradation in the early periods, but some molecules of CRAM are selectively degraded by microorganisms in the final period. The growth of cyanobacterial lead to increasing the concentration of protein-like and carbohydrate-like molecule of DOM in the water. In the final stage, the molecule group of CHO disappear significantly and the molecule group of heteroatomic group increase.

Face mask derived micro(nano)plastics and organic compounds potentially induce threat to aquatic ecosystem security revealed by toxicogenomics-based assay.

Micro(nano)plastics widely detected in aquatic environments have caused serious threat to water quality security. However, as a potential important source of micro(nano)plastics in surface water during the COVID-19 pandemic, the ecological risks of face mask waste to aquatic environments remain poorly understood. Herein, we comprehensively characterized the micro(nano)plastics and organic compounds released from four daily used face masks in aqueous environments and further evaluated their potential impacts on aquatic ecosystem safety by quantitative genotoxicity assay. Results from spectroscopy and high-resolution mass spectrum showed that plastic microfibers/particles (∼11%-83%) and leachable organic compounds (∼15%-87%) were dominantly emitted pollutants, which were significantly higher than nanoplastics (< ∼5%) based on mass of carbon. Additionally, a toxicogenomics approach using green fluorescence protein-fused whole-cell array revealed that membrane stress was the primary response upon the exposure to micro(nano)plastics, whereas the emitted organic chemicals were mainly responsible for DNA damage involving most of the DNA repair pathways (e.g., base/nucleotide excision repair, mismatch repair, double-strand break repair), implying their severe threat to membrane structure and DNA replication of microorganisms. Therefore, the persistent release of discarded face masks derived pollutants might exacerbate water quality and even adversely affect aquatic microbial functions. These findings would contribute to unraveling the potential effects of face mask waste on aquatic ecosystem security and highlight the necessity for more developed management regulations in face mask disposal.

High expression of LOC541471, GDAP1, SOD1, and STK25 is associated with poor overall survival of patients with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is an aggressive heterogeneous hematological malignancy with remarkably heterogeneous outcomes. This study aimed to identify potential biomarkers for AML risk stratification via analysis of gene expression profiles. METHODS: RNA sequencing data from 167 adult AML patients in the Cancer Genome Atlas (TCGA) database were obtained for overall survival (OS) analysis, and 52 bone marrow (BM) samples from our clinical center were used for validation. Additionally, siRNA was used to investigate the role of prognostic genes in the apoptosis and proliferation of AML cells. RESULTS: Co-expression of 103 long non-coding RNAs (lncRNAs) and mRNAs in the red module that were positively correlated with European Leukemia Network (ELN) risk stratification and age was identified by weighted gene co-expression network analysis (WGCNA). After screening by uni- and multivariate Cox regression, Kaplan-Meier survival, and protein-protein interaction analysis, four genes including the lncRNA LOC541471, GDAP1, SOD1, and STK25 were incorporated into calculating a risk score from coefficients of the multivariate Cox regression model. Notably, GDAP1 expression was the greatest contributor to OS among the four genes. Interestingly, the risk score, ELN risk stratification, and age were independent prognostic factors for AML patients, and a nomogram model constructed with these factors could illustrate and personalize the 1-, 3-, and 5-year OS rates of AML patients. The calibration and time-dependent receiver operating characteristic curves (ROCs) suggested that the nomogram had a good predictive performance. Furthermore, new risk stratification was developed for AML patients based on the nomogram model. Importantly, knockdown of LOC541471, GDPA1, SOD1, or STK25 promoted apoptosis and inhibited the proliferation of THP-1 cells compared to controls. CONCLUSIONS: High expression of LOC541471, GDAP1, SOD1, and STK25 may be biomarkers for risk stratification of AML patients, which may provide novel insight into evaluating prognosis, monitoring progression, and designing combinational targeted therapies.

[Molecular Signatures of Dissolved Organic Matter in the Paihe River and Its Tributaries].

Dissolved organic matter (DOM) is an abundant and critical component of aquatic ecosystems, participating in many physicochemical and biogeochemical processes. The Paihe River is the only inflow river in the Jianghuai section of "Yangtze-Huaihe water diversion" clear water gallery project; however, its DOM molecular composition information and characteristics are still unclear. In this study, the molecular characterization of DOM in the Paihe River and Guangming Dayan River was determined using Orbitrap mass spectrometry. The Pearson's correlation and principal component analysis (PCA) were used to study the relationship between molecular composition information, characteristics, and sources of DOM in two rivers. The results showed that the molecular weight and oxygen content of DOM molecules in the Paihe River were relatively low; the molecular weight, aromaticity, and unsaturation of DOM molecules in the Guangming Dayan River were relatively high. From the element composition and compound composition of the two rivers' DOM, both rivers were mainly composed of CHO-compounds, lignin, and tannins derived from land plants, which indicates that both rivers were severely affected by terrestrial input. There were high percentages of CHOS, protein, and lipid compounds of DOM in the Paihe River. According to the results of the Pearson's correlation and PCA analyses, the DOM molecules of the Paihe River were also influenced by wastewater from sewage treatment plants, urbanization processes, and microbial activity. Molecular composition information and characteristics of DOM can provide a detailed reference to improve the theoretical support for the Paihe River clear water gallery project.

Abnormal vibration perception threshold alters the gait features in type 2 diabetes mellitus patients.

Objective: It is generally believed that gait characteristics of diabetic neuropathic patients differ from those of non-diabetic ones. However, it is still unclear how the abnormal foot sensation influences the gait during walking in type 2 diabetes mellitus (T2DM). For the purpose of gaining a better insight into the alterations of detailed gait parameters and figuring out important aspects in the gait indexes by peripheral neuropathy in elder T2DM patients, we compared the gait features in participants with normal glucose tolerance (NGT) controls and diabetic individuals complicated by peripheral neuropathy or not. Subjects and methods: Gait parameters were observed during the 10-m walk on flat land among different conditions of diabetes in 1,741 participants from three clinical centers. Subjects were divided into four groups: persons with NGT were taken as the control group; patients with T2DM included three subgroups: DM control (no chronic complications), DM-DPN (DM complicated by only peripheral neuropathy), and DM-DPN+LEAD (DM complicated by both neuropathy and artery disease). The clinical characteristics and gait parameters were assessed and compared among these four groups. Analyses of variance were employed to verify possible differences of gait parameters between groups and conditions. Stepwise multivariate regression analysis was performed to reveal possible predictors of gait deficits. Receiver operating characteristic (ROC) curve analysis was employed to find any discriminatory power of diabetic peripheral neuropathy (DPN) for the step time. Results: In participants burdened with DPN, whether complicated by lower extremity arterial disease (LEAD) or not, step time increased sharply (p < 0.05). Stepwise multivariate regression models showed that independent variables of gait abnormality were sex, age, leg length, vibration perception threshold (VPT), and ankle-brachial index (ABI) (p < 0.01). Meanwhile, VPT was a significant independent predictor of step time, spatiotemporal variability (SDA), and temporal variability (SDB) (p < 0.05). ROC curve analysis was explored to find the discriminatory power of DPN for the occurrence of increased step time. The area under the curve (AUC) value was 0.608 (95% CI: 0.562-0.654, p < 0.01), and the cutoff point was 538.41 ms accompanied by a higher VPT. A significant positive association was observed between increased step time and the highest VPT group [odds ratio (OR) = 1.83, 95% CI: 1.32-2.55, p< 0.01]. In female patients, this OR value elevated to 2.16 (95% CI: 1.25-3.73, p< 0.01). Conclusions: In addition to sex, age, and leg length, VPT was a distinct factor that associated with altered gait parameters. DPN is associated with increased step time, and the step time increases with worsening VPT in type 2 diabetes.

Establishment of hairy root culture of Rubia yunnanensis Diels: Production of Rubiaceae-type cyclopeptides and quinones.

Rubia yunnanensis is an important medicinal plant with various bioactive secondary metabolites. In order to reduce the dependence on wild populations of the species, we aim to establish in vitro culture system that can produce Rubiaceae-type cyclopeptides (RAs) and quinones. Agrobacterium rhizogenes-mediated transformation of stem segments of in vitro grown R. yunnanensis plants using four A. rhizogenes strains was studied and transformation conditions were optimized. Hairy roots appeared with the highest frequency (68.89%) when stem segments (with leaves) without pre-culture were immersed in A. rhizogenes A4 strain bacterial suspension for 30 min, co-cultured on Murashige and Skoog (MS) solid medium in the dark for three days, and afterwards incubated in darkness. PCR analysis of rolB and rolC genes confirmed transformed nature of six hairy root clones. The hairy roots grew rapidly, especially showing the highest accumulation of biomass in MS liquid medium compared to in vitro grown plants and calli. Histological observation of hairy root revealed anatomical difference in vascular cylinder, where the cells exhibited high mitotic activity characterized by vigorous growth. The UPLC-MS/MS analysis revealed that the amount of RAs in the hairy roots grown in ½MS liquid medium (4.611 µg g-1 DW) was higher than that in in vitro grown plants (0.331 and 4.096 µg g-1 DW for shoots and roots respectively) and calli (1.082 µg g-1 DW), but still far lower than that in the roots of seed-borne plants (80.296 µg g-1 DW). However, the hairy roots accumulated high level of quinones (2320.923 and 5067.801 µg g-1 DW for MS and ½MS liquid media respectively), of the same order of magnitude as the roots of seed-borne plants (7409.973 µg g-1 DW). Hairy root culture of R. yunnanensis, with high accumulation of biomass and production of quinones, may offer an attractive perspective for the production of the RAs and quinones that could be further optimized for pharmaceutical use.

Computational design and synthesis of molecular imprinted polymers for selective solid phase extraction of sulfonylurea herbicides.

A high-efficiency approach for the synthesis of molecularly imprinted polymers has been developed and further for the solid-phase extraction of sulfonylurea herbicides in food samples. Molecular simulation approach combined chemometric selected metsulfuron-methyl (MSM) and 2-trifluoromethyl acrylic acid (TFMAA) as the template and the monomer to synthesize the molecularly imprinted polymers (MIPs). Experimental validation confirmed that the MSM-imprinted polymers showed a higher selectivity and affinity to sulfonylurea herbicides. The optimized molecularly imprinted solid-phase extraction (MISPE) conditions, including loading, washing, and eluting conditions, were established. The developed MISPE technology combined HPLC-MSMS was successfully used for the determination of sulfonylurea herbicides in foods. Compared with commercial SPE columns, MISPE showed high affinity, excellent selectivity and low matrix effect. The recoveries of sulfonylurea herbicides spiked in four matrices were between 86.4% and 100.2%, with the relative standard deviations (RSD) in the range of 0.9%-10.5%.

Chemical speciation of ciprofloxacin in aqueous solution regulates its phytotoxicity and uptake by rice (Oryza sativa L.).

Ciprofloxacin (CIP), a widely used fluoroquinolone antibiotic, is frequently detected in aqueous environments, and could be assimilated by vegetable plants to possess potential threats to human and animal health through food chains. However, plant uptake of CIP in different chemical speciation has still far from clear now. Thus, the toxicity and uptake of CIP by rice plants were investigated under different solution pH, owing to its contribution to different chemical speciation of CIP. Results display that high pH-driven changes of CIP from cation (CIP+) to anion (CIP-) decreased its adsorption and uptake by excised roots and intact plants, respectively. However, CIP concentrations in roots, stems and leaves all exhibited no significant differences with increasing solution pH. Moreover, six intermediates of CIP were detected and two possible transformation pathways were proposed in rice plants, including firstly oxidation and following consecutive cleavage of piperazine ring. After accumulated in plant tissues, CIP significantly inhibited the plant growth, decreased the photosynthetic pigments contents and enhanced the antioxidant enzyme activities in a concentration-dependent manner. Besides, high pH exacerbated the growth inhibition and changed the oxidative damage responses of rice plants to CIP. These findings indicate that the uptake and toxicity of CIP in rice plants were influenced by solution pH-driven changes of its chemical speciation.

Application of Chemometrics for Coal Pyrolysis Products by Online py-GC×GC-MS.

Investigations on the molecular composition of coal pyrolysis products can help us to improve nonfuel utilization of coal. Meanwhile, the molecular composition of coal pyrolysis products is also influenced by the characteristics and depositional environment of coal. However, due to the extremely complex nature of coal, direct investigation of the molecular composition of coal pyrolysis products is still a challenge. In the present work, the data of the molecular composition of bituminous coal pyrolysis products are obtained by online pyrolysis coupled to comprehensive two-dimensional gas chromatography and mass spectrometry (online py-GC×GC-MS) and are divided into nine molecular groups depending on the aromaticity of the pyrolysis products and separating power of the GC×GC-MS. Chemometric tools, hierarchical cluster analysis, and principal component analysis are employed to reveal the correlations among the molecular composition of coal pyrolysis products and coal characteristics. The results show that the nine molecular groups of bituminous coal pyrolysis products can be divided into two clusters, the "aromatic group" and the "aliphatic group", and that the eight coals are divided into three clusters, all of which can be interpreted by the depositional environments and δ13CVPDB values of coals. Moreover, a simple and empirical equation for estimation of coal tar from hydropyrolysis can be obtained depending on the chemometric results of the molecular composition of the coal pyrolysis products. By application of chemometrics, the molecular composition of coal pyrolysis products can provide preference to industrial utilization of coal.

Alkyl chain length affecting uptake of imidazolium based ionic liquids by ryegrass (Lolium perenne L.).

Imidazolium based ionic liquids (ILs) have been extensively used in the various industrial fields, however, the dependence of their structure on toxicity and bioavailability by plants is not clear. Thus, in this study, uptake of imidazolium based ILs with different alkyl chain lengths (e.g., [C2mim]+ and [C8mim]+) by ryegrass and their toxicity to plant growth were investigated. Results show that the two ILs could be removed by ryegrass with high efficiencies, and a higher uptake efficiency and accumulation was observed for [C2mim]+ with shorter chain length compared with that for [C8mim]+. A higher growth inhibition of ryegrass by [C8mim]+ was observed compared with that by [C2mim]+, indicating the long alkyl chain length of ILs had a negative effect on the plant growth. ILs taken up by ryegrass was retained in the roots and their translocation from roots to shoots was restricted. The IL concentration in roots was 0.68 mg/g-fresh weight for [C2mim]+ and 0.08 mg/g- fresh weight for [C8mim]+ when the ryegrass was exposed to 10 mg/L ILs. This study proved that plant assimilation of ILs depended on their alky chain lengths, which would be useful for understanding the fate of ILs with various structures in phytoremediation for ILs-contaminated water.

Concentration- and nutrient-dependent cellular responses of microalgae Chlorella pyrenoidosa to perfluorooctanoic acid.

Perfluorooctanoic acid (PFOA), an emerging and persistent pollutant, could cause toxicity effects on aquatic organisms. However, this was generally assessed under high exposure concentrations of PFOA and nutrient-enriched conditions, which was not accordant with the actual environments. Therefore, to comprehensively understand the toxicity effects of PFOA on aquatic organisms, the cellular responses of microalgae, Chlorella pyrenoidosa, to PFOA under different concentrations (≤ 1.0 mg/L) and nutrient conditions were investigated in this study. Results show that PFOA at concentrations less than 1.0 mg/L had no significant effects on algal growth and chlorophyll contents, and no oxidative damages were generated to destroy membrane integrity and morphology. However, N,P-limited and -starved conditions significantly decreased algal growth and chlorophyll contents, and induced oxidative stresses to ruin the structure and function of cell membrane. Moreover, the deficiency of P had more severe negative effect on algae than that of N, and they both influenced the toxicity responses of microalgae to 1.0 mg/L PFOA. The adsorption and uptake percentages of PFOA by algal cells were both less than 10%, and increased adsorption but decreased uptake of PFOA amounts occurred under N,P-limited and -starved conditions. These findings will be useful to understand the toxicity effects of PFOA on microalgae in aquatic environments.

Qualitative and quantitative analyses of quinones in multi-origin Rubia species by ultra-performance liquid chromatography-tandem mass spectrometry combined with chemometrics.

Rubia species are one of the important multi-origin phytomedicines having both economical and medicinal values in many countries. Quinones are the predominant bioactive constituents of these species. Therefore, accurate analysis of these quinones is critical to quality control, clinical, and commercial applications of Rubia species. In this study, a sensitive and efficient ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method in positive and negative multiple reaction monitor (+/-MRM) modes was firstly developed for the characterization of 45 quinones and the quantification of 24 quinones from Rubia plants. The chromatographic separation was achieved on a Waters ACQUITY UPLC® BEH C18 column by using a gradient elution with a mobile phase consisting of 0.1 % formic acid in water and acetonitrile. The results indicated that quinones in multi-origin Rubia samples were different, but 10 quinones existed in all samples. R. cordifolia, which is a unique official medicinal material in Chinese Pharmacopeia, contained the most number of quinones among all the Rubia species. R. podantha and R. sylvatica had the next highest number of quinones, implying that these species could be used as alternatives for R. cordifolia. Chemometric approaches were applied to evaluate the chemical relationship between the Rubia samples based on the constituent quinones. In this study, a UPLC-QqQ-MS/MS method in the MRM mode has been developed for the analysis of Rubia species-derived quinones, which not only contributes to quality control and discrimination of Rubia species, but also suggests the potential of these species in clinical and commercial applications.

Magnetic C60 nanospheres based solid-phase extraction coupled with isotope dilution gas chromatography-mass spectrometry method for the determination of sixteen polycyclic aromatic hydrocarbons in Chinese herbal medicines.

C60-based magnetic nanospheres were synthesized by coating Fe3O4 nanospheres with silica, then modifying with 3-aminopropyltriethoxysilane as a linker and a C60 fullerene stationary phase. The morphologies, magnetic properties, infrared absorption and carbon content of magnetic nanospheres were studied by TEM, VSM, FTIR and carbon and sulfur analyzer. The magnetic nanospheres were employed for the magnetic solid-phase extraction (MSPE) of 16 polycyclic aromatic hydrocarbons (PAHs) in nine Chinese herbal medicines. The analyses were conducted by isotope dilution gas chromatography-mass spectrometry. The main parameters influencing the extraction, including extraction solvent, adsorbent amount, and extraction time were optimized. Method validation showed that the limit of detection (LOD) was 0.02-0.11 µg/kg, and the limit of quantification (LOQ) was 0.07-0.36 µg/kg. The spiked recoveries rates for 16 PAHs in white peony root were 84.7-107.2%. The relative standard deviation (RSD) was 1.7-8.4%. The established method was further used for the determination 16 PAHs in nine Chinese herbal medicines. Total content of 16 PAHs varied from 73.6 µg/kg (fructus lycii) to 2172.6 µg/kg (astragalus root). The results indicate that the pollution of PAHs in Chinese herbal medicines is serious. The established method can effective detect PAHs contamination in Chinese herbal medicines.

Mixture toxicity and uptake of 1-butyl-3-methylimidazolium bromide and cadmium co-contaminants in water by perennial ryegrass (Lolium perenne L.).

Ionic liquids, a kind of emerging and persistent organic contaminants, always coexist with heavy metals in aquatic and terrestrial environments. However, the feasibility of phytoremediation to remove ionic liquids and heavy metals co-contaminants is still unclear. Thus, in this study, the hydroponic experiment was conducted to investigate the combined effect of 1-butyl-3-methylimidazolium bromide ([C4mim]+Br-) and cadmium (Cd2+) on growth and physiological indictors of perennial ryegrass, together with their uptake and translocation by plants. Results show that the exposure of ryegrass to [C4mim]+ and Cd2+ mixture significantly inhibited the biomass growth and affected the photosynthetic pigments contents in leaves. The increases of lipid peroxidation and catalase, peroxidase activity were also observed under the co-exposure experiments. The mixture toxicity of [C4mim]+ and Cd2+ to ryegrass growth showed an additive effect predicted by concentration addition and independent action. [C4mim]+ uptake and acropetal translocation by ryegrass were significantly inhibited with dosing Cd2+. In contrast, [C4mim]+ had no obvious effect on Cd2+ uptake by ryegrass, while enhanced Cd2+ translocation from roots to shoots occurred with increasing [C4mim]+ dosages. These results indicate that the co-contamination of ionic liquids and heavy metals would affect their fates during phytoremediation.

Sustained ER stress promotes hyperglycemia by increasing glucagon action through the deubiquitinating enzyme USP14.

Endoplasmic reticulum (ER) stress plays an important role in metabolic diseases like obesity and type 2 diabetes mellitus (T2DM), although the underlying mechanisms and regulatory pathways remain to be elucidated. Here, we induced chronic low-grade ER stress in lean mice to levels similar to those in high-fat diet (HFD)-fed obese mice and found that it promoted hyperglycemia due to enhanced hepatic gluconeogenesis. Mechanistically, sustained ER stress up-regulated the deubiquitinating enzyme ubiquitin-specific peptidase 14 (USP14), which increased the stability and levels of 3',5'-cyclic monophosphate-responsive element binding (CREB) protein (CBP) to enhance glucagon action and hepatic gluconeogenesis. Exogenous overexpression of USP14 in the liver significantly increased hepatic glucose output. Consistent with this, liver-specific knockdown of USP14 abrogated the effects of ER stress on glucose metabolism, and also improved hyperglycemia and glucose intolerance in obese mice. In conclusion, our findings show a mechanism underlying ER stress-induced disruption of glucose homeostasis, and present USP14 as a potential therapeutic target against T2DM.

TAL1 mediates imatinib-induced CML cell apoptosis via the PTEN/PI3K/AKT pathway.

Chronic myeloid leukemia (CML) is associated with chromosomal translocation t(9; 22), which results in formation of the BCR-ABL oncogene. CML is treated with tyrosine kinase inhibitors (TKIs), which target BCR-ABL, to eradicate BCR-ABL + cells. However, the TKI imatinib (IM) fails to eliminate quiescent leukemia stem cells (LSCs) in CML. In this study, we demonstrate that transcription factor TAL1 is down-regulated in CML LSCs by BCR-ABL, and IM triggers TAL1 mRNA expression. In addition, loss of TAL1 abrogates IM-induced CML cell apoptosis. RNA-seq analysis suggests that TAL1 expression may affect PI3K/AKT pathway. Moreover, depletion of TAL1 inhibits the expression of PTEN, which is a negative regulator of the PI3K/AKT pathway. Our results reveal an unexpected involvement of TAL1 in CML etiology and demonstrate that TAL1 may regulate PTEN expression and lead to inhibition of the PI3K/AKT pathway in the response of CML cells to TKI. These results implicate regulation of PTEN expression as a novel mechanism for the transcriptional regulatory networks of TAL1 in CML.

The c-Myc-regulated miR-17-92 cluster mediates ATRA-induced APL cell differentiation.

BACKGROUND: Despite advances in the treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA), its underlying mechanism has not been fully elucidated. The oncogenic microRNA cluster miR-17-92 modulates multiple cellular processes, including survival, proliferation, and apoptosis. However, the role of miR-17-92 and its regulation has not yet been documented for APL. METHODS: We analyzed miR-17-92 expression in APL samples and cell lines by qRT-PCR. The expression of c-Myc was measured by western blot. Cell differentiation was assessed by measuring the surface CD11b antigen expression by flow cytometry analysis. RESULTS: We observed that miR-17-92 was upregulated in APL compared with healthy donors. Furthermore, we demonstrated that expressions of c-Myc and miR-17-92 are markedly suppressed during ATRA-induced NB4 cell differentiation. Importantly, we also demonstrated that miR-17-92 is directly regulated by c-Myc during the granulocytic differentiation of APL cells. Finally, the overexpression of miR-17-5p blocks ATRA-induced differentiation. CONCLUSIONS: We report abnormal expression of the miR-17-92 cluster in APL cells, which is responsible for the differentiation block in blast cells in APL. In addition, we identified miR-17-92 as a target gene of c-Myc during ATRA-induced granulocytic differentiation.

Colletopeptides A-D, Anti-inflammatory Cyclic Tridepsipeptides from the Plant Endophytic Fungus Colletotrichum sp. S8.

Four new hybrid peptide-polyketide cyclic tridepsipeptides, colletopeptides A-D (1-4), were isolated and characterized from the endophytic fungus Colletotrichum sp. S8 derived from the stems of Rubia podantha with the guidance of LC-UV-MS detection. Their structures were elucidated by extensive spectroscopic analysis and X-ray crystallography. Compounds 1-4 are rare natural 12-membered cyclic tridepsipeptides containing a 3,5,11-trihydroxy-2-methyl dodecanoic acid unit in their structures. 1-4 inhibited lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages with the IC50 values of 8.3, 38.7, 13.5, and 22.2 µM, respectively. 1 also inhibited the production of inflammatory factors IL-6 and TNF-α, and decreased the phosphorylation of NF-κB-associated proteins IκBα and p65.

Uptake, accumulation and metabolization of 1-butyl-3-methylimidazolium bromide by ryegrass from water: Prospects for phytoremediation.

The unique properties of ionic liquids make them attractive for a wide range of industrial applications, which makes it easy to be released into the environment and cause water or soil pollution. Phytoremediation of organic contaminants is a safe and important process for removing persistent pollutants from the environment. However, due to they are very chemically stable and potentially toxic to plants, whether they can be removed, assimilated and metabolized by plants remains unknown during phytoremediation process. In this study, ryegrass, Lolium perenne L., was used for imidazolium ionic liquid (1-butyl-3-methylimidazolium bromide, [C4mim]+) removal from water. The results show that [C4mim]+ could be taken up, accumulated and metabolized by plants in vivo with a high removal efficiency. Most of the [C4mim]+ was accumulated in the root tissue, with the root concentration fraction factors ranging from 4.9 to 51.5. Two hydroxylated metabolites 1-(4-hydroxybutyl)-3-methylimidazolium, and 1-(n-butyl)-3-(hydroxymethyl)-imidazolium, and two secondary metabolites were detected in the ryegrass after [C4mim]+ uptake. The metabolic mechanism was clarified using density functional theory calculations. Furthermore, [C4mim]+ at a high concentration was found to be high toxic to inhibit the growth of ryegrass markedly. In response, some oxidative stress was observed in the metabolic process, as indicated by increasing of catalase, super dismutase and peroxidase activities. Our results suggested that phytoremediation was an efficient technique for ionic liquids treatment from water.