Purpose
Phytostabilization is known to be a promising technique to prevent the off-site movement of cadmium (Cd) from severely contaminated arable soils. Previous studies have recognized plants and ...amendments that could be potentially used for phytostabilization, such as non-edible fiber and energy crops and biochar. However, there is a paucity of information on the performance of these candidate crops and amendments for the application in the field.
Methods
Twelve plant-amendment systems were established on the farmland severely contaminated with Cd in the South China karst area, which comprises cash crops kenaf (
Hibiscus cannabinus
), ramie (
Boehmeria nivea
), and sorghum (
Sorghum bicolor
) together with the application of lime, coconut shell biochar, and rice straw biochar at different rates. A comprehensive score was introduced to evaluate the performance of the studied plant-amendment systems, considering not only the indicators related to soil Cd mobility but also the costs.
Results
After one crop cycle, a 40% median rate of reduction was achieved in soil available Cd. An intensive application of biochar lowered the comprehensive performance since a significantly increased cost gained only a slight improvement in the reduction of soil available Cd. Sorghum with 0.5% (
w
/
w
) rice straw biochar showed the best performance in the study site, which effectively sequestrated Cd in the roots and reduced soil available Cd at a relatively low cost.
Conclusion
This work shows the performance and the comprehensive evaluation of candidate plant-amendment systems for the in situ phytostabilization.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose: Hepatocellular carcinoma (HCC), a common cancer worldwide, has a dismal outcome partly due to the poor identification of
early-stage HCC. Currently, one third of HCC patients present with ...low serum α-fetoprotein (AFP) levels, the only clinically
available diagnostic marker for HCC. The aim of this study was to identify new diagnostic molecular markers for HCC, especially
for individuals with low serum AFP.
Experimental Design: We used the microarray technique to determine the expression profiles of 218 HCC specimens from patients with either high
or low serum AFP. From the microarray study, we selected five candidate genes (i.e., GPC3, PEG10, MDK, SERPINI1 , and QP-C ), which were overexpressed in HCCs. Using quantitative real-time PCR analyses, we validated the expression of these five
genes in 50 AFP-normal and 8 AFP-positive HCC specimens and 36 cirrhotic noncancerous hepatic specimens, which include 52
independent specimens not used in microarray analysis.
Results: A significant increase in the expression of the five candidate genes could be detected in most of the HCC samples, including
those with normal serum AFP and small tumors. GPC3, MDK , and SERPINI1 encode known serum proteins. Consistently, a significant increase in serum midkine, encoded by MDK , was associated with HCC patients, including those with normal serum AFP. Using prediction analysis of microarray, we showed
that a combined score of these five genes can accurately classify noncancerous hepatic tissues (100%) and HCC (71%).
Conclusions: We suggest that a diagnostic signature approach using a combined score of these five biomarkers rather than a single marker
may improve the prediction accuracy of HCC patients, including those with normal serum AFP and smaller-sized tumors.
Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based ...applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model.
We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models.
We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.
Accurate and sensitive detection of single-base mutations in RNAs is of great value in basic studies of life science and medical diagnostics. However, the current available RNA detection methods are ...challenged by heterogeneous clinical samples in which trace RNA mutants usually existed in a large pool of normal wild sequences. Thus, there is still great need for developing the highly sensitive and highly specific methods in detecting single-base mutations of RNAs in heterogeneous clinical samples. In the present study, a new chimeric DNA probe-aided ligase chain reaction-based electrochemical method (cmDNA-eLCR) was developed for RNA mutation detection through the BSA-based carrier platform and the horseradish peroxidase-hydrogen peroxide-tetramethylbenzidine (HRP-H2O2-TMB) system. The denaturing polyacrylamide gel electrophoresis and a fluorophore-labeled probe was ingeniously designed to demonstrate the advantage of cmDNA in ligation to normal DNA templated by RNA with the catalysis of T4 RNA ligase 2 as well as its higher selectivity than DNA ligase system. Finally, the proposed cmDNA-eLCR, compared with the traditional eLCR, showed excellent performance in discriminating single base-mismatched sequences, where the signal response for mismatched targets at a high concentration could overlap completely with that for the blank control. Besides, this cmDNA-eLCR assay had a wide linear range crossing six orders of magnitude from 1.0 × 10–15 to1.0 × 10–10 M with a limit of detection as low as 0.6 fM. Furthermore, this assay was applied to detect RNA in real sample with a satisfactory result, thereby demonstrating its great potential in diagnosis of RNA-related diseases.
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IJS, KILJ, NUK, PNG, UL, UM
Background & Aims Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis mainly due to metastasis. MicroRNAs are endogenous small noncoding RNAs that regulate cellular gene ...expression and are functionally linked to tumourigenesis. Using microarray analysis, we recently identified 20 miRNAs associated with HCC metastasis. Here, we carried out further analyses on one of these microRNAs, let-7g, to determine whether it is functionally linked to HCC metastasis. Methods Quantitative real-time polymerase chain reaction was used to determine the level of mature let-7g transcript in HCC clinical specimens and its correlation with patient survival. Ectopic expression of let-7g was carried out in HCC cell lines to assess its influence on cell growth, migration, and invasion. Results We confirmed that the level of let-7g was significantly lower in metastatic HCCs compared to metastasis-free HCCs. Moreover, low let-7g expression in a tumour was predictive of poor survival in HCC patients. Functional studies indicated that ectopic expression of let-7g significantly inhibits HCC cell migration and cell growth. In-silico analysis revealed members of soluble collagens as potential targets of let-7g. Consistently, the levels of type I collagen α2 (COL1A2) and let-7g were inversely correlated in HCC clinical specimens. COL1A2 was experimentally validated as a direct target of let-7g. Moreover, addition of COL1A2 counteracted the inhibitory effect of let-7g on cell migration. Conclusions These results suggest that let-7g may suppress HCC metastasis partially through targeting COL1A2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Global climate change has exacerbated flooding in coastal areas affected by soil salinization. Ammonium (NH4+) is the predominant form of nitrogen in flooded soils, but the role played by NH4+ in the ...plant response to salt stress has not been fully clarified. We investigated the responses of Arabidopsis thaliana, Oryza sativa, and Nicotiana benthamiana plants fed with NH4+. All species were hypersensitive to NaCl stress and accumulated more Cl− and less Na+ than those fed with NO3−. Further investigation of A. thaliana indicated that salt hypersensitivity induced by the presence of NH4+ was abolished by removing the Cl− but was not affected by the removal of Na+, suggesting that excess accumulation of Cl− rather than Na+ is involved in NH4+-conferred salt hypersensitivity. The expression of nitrate transporter NRT1.1 protein was also up-regulated by NH4+ treatment, which increased root Cl− uptake due to the Cl− uptake activity of NRT1.1 and the absence of uptake competition from NO3−. Knockout of NRT1.1 in plants decreased their root Cl− uptake and retracted the NH4+-conferred salt hypersensitivity. Our findings revealed that NH4+-aggravated salt stress in plants is associated with Cl− over-accumulation through the up-regulation of NRT1.1-mediated Cl− uptake. These findings suggest the significant impact of Cl− toxicity in flooded coastal areas, an issue of ecological significance.
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•The plants are hypersensitive to salt stress in NH4+ medium due to Cl− uptake.•Excess of Cl− in plants grown in NH4+ medium is associated with the Cl- uptake by NRT1.1.•The impact of Cl− toxicity in flooded-coastal areas requires serious consideration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Rarely reported KMT2D, FAT1, and RELN mutations were detected at high frequencies in Chinese AML patients for the first time.•The gene mutation spectrum of older patients was markedly different to ...that of younger patients.•Older patients harbored more SRSF2 mutations, which predicted lower rates of overall and relapse-free survival.
Differences in the gene mutation spectra of younger and older Chinese adult AML patients and the prognostic significance of these differentially presented gene mutations are rarely reported. One hundred and thirteen newly diagnosed Chinese adults with AML, divided into groups of younger and older patients, were enrolled in this study. Bone marrow samples from the patients were analyzed using targeted next-generation sequencing with a panel of 141 genes. Ninety-eight mutated genes were detected and the top 10 mutated genes were KMT2D, FLT3, FAT1, ASXL1, NRAS, DNMT3A, RELN, TET2, JAK2, and KRAS. The top five functional groups were the tyrosine kinase pathway, transcription factors, DNA methylation, chromatin modifiers, and the JAK-STAT signaling pathway. Younger patients exhibited higher incidences of KMT2D (33.8% vs 10.4%, P = 0.004) and KRAS (15.4% vs 2.1%, P = 0.042) mutations than older patients; whereas, older patients harbored more SRSF2 (20.8% vs 0%, P = 0.002), transcription factor (85.4% vs 67.7%, P = 0.031), DNA methylation (58.3% vs 36.9%, P = 0.024), and RNA splicing (31.3% vs 12.3%, P = 0.013) mutations than younger patients. Moreover, patients with SRSF2 mutations exhibited a lower rate of overall survival (P < 0.001) and relapse-free survival (P < 0.001) than patients carrying wild-type SRSF2. In conclusion, rarely reported KMT2D, FAT1, and RELN mutations were detected at high frequencies in our cohort. The gene mutation spectrum of older patients was different to that of younger patients. Moreover, older patients harbored more SRSF2 mutations, which predicted lower rates of overall and relapse-free survival.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Prostate cancer is the second most common cancer in men worldwide
. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing ...its genetic and epigenetic landscape in thousands of patients
. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis ...(HD) patients.
Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death.
We recruited 252 patients and divided them into a high-TMAO group (>4.73 μg/mL) and a low-TMAO group (≤4.73 μg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001).
High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Acidosis, a common feature of cerebral ischaemia and hypoxia, plays a key role in these pathological processes by aggravating the ischaemic and hypoxic injuries. To explore the mechanisms, in this ...research, we cultured primary neurons in an acidic environment (potential of hydrogen pH6.2, 24 hours) to mimic the acidosis. By proteomic analysis, 69 differentially expressed proteins in the acidic neurons were found, mainly related to stress and cell death, synaptic plasticity and gene transcription. And, the acidotic neurons developed obvious alterations including increased neuronal death, reduced dendritic length and complexity, reduced synaptic proteins, tau hyperphosphorylation, endoplasmic reticulum (ER) stress activation, abnormal lysosome‐related signals, imbalanced oxidative stress/anti‐oxidative stress and decreased Golgi matrix proteins. Then, melatonin (1 × 10−4 mol/L) was used to pre‐treat the cultured primary neurons before acidic treatment (pH6.2). The results showed that melatonin partially reversed the acidosis‐induced neuronal death, abnormal dendritic complexity, reductions of synaptic proteins, tau hyperphosphorylation and imbalance of kinase/phosphatase. In addition, acidosis related the activations of glycogen synthase kinase‐3β and nuclear factor‐κB signals, ER stress and Golgi stress, and the abnormal autophagy‐lysosome signals were completely reversed by melatonin. These data indicate that melatonin is beneficial for neurons against acidosis‐induced injuries.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK