Cadmium tolerance and accumulation from the perspective of metal ion absorption and root exudates in broomcorn millet.

Cadmium (Cd) is a persistent heavy metal that poses environmental and public health concerns. This study aimed to identify the potential biomarkers responsible for Cd tolerance and accumulation by investigating the response of the content of essential metal elements, transporter gene expression, and root exudates to Cd stress in broomcorn millet (Panicum miliaceum). A hydroponics experiment was conducted using two broomcorn millet cultivars with distinct Cd tolerance levels and accumulation phenotypes (Cd-tolerant and Cd-sensitive cultivars). Cd stress inhibited lateral root growth, especially in the Cd-sensitive cultivar. Furthermore, Cd accumulation was significantly greater in the Cd-tolerant cultivar than in the Cd-sensitive cultivar. Cd stress significantly inhibited the absorption of essential metal elements and significantly increased the calcium concentration. Differentially expressed genes involved in metal ion transport were identified via transcriptome analysis. Cd stress altered the composition of root exudates, thus increasing lipid species and decreasing alkaloid, lignan, sugar, and alcohol species. Moreover, Cd stress significantly reduced most alkaloid, organic acid, and phenolic acid exudates in the Cd-tolerant cultivar, while it increased most lipid and phenolic acid exudates in the Cd-sensitive cultivar. Some significantly changed root exudates (ferulic acid, O-coumaric acid, and spermine) are involved in the phenylalanine biosynthesis, and arginine and proline metabolic pathways, thus, may be potential biomarkers of Cd stress response. Overall, metal ion absorption and root exudates are critical for Cd tolerance and accumulation in broomcorn millet. These findings provide valuable insights into improving Cd phytoremediation by applying mineral elements or metabolites.

Dynamic and Comparative Transcriptome Analyses Reveal Key Factors Contributing to Cadmium Tolerance in Broomcorn Millet.

Broomcorn millet (Panicum miliaceum L.) has great potential in Cd phytoextraction, but its mechanisms are largely unknown. Two contrasting broomcorn millet varieties, 'Ningmi6' (Cd-sensitive variety) and '4452' (Cd-tolerant variety), were investigated through morphological, physiological, and transcriptomic analyses to determine the factors responsible for their differential Cd tolerance and translocation. The Cd-tolerant variety can accumulate more Cd, and its cell wall and vacuole component Cd proportions were higher compared with the Cd-sensitive variety. Under Cd stress, the glutathione content and peroxidase activity of the Cd-tolerant variety were significantly higher than those of the Cd-sensitive variety. Additionally, weighted gene co-expression network analysis (WGCNA) revealed hub modules that were associated with Cd stress and/or variety. Notably, genes involved in these hub modules were significantly enriched for roles in glutathione metabolism, phenylpropanoid biosynthesis, ABC transport, and metal ion transport process. These results suggested that regulation of genes associated with cell wall precipitation and vacuole compartmentalization may increase Cd tolerance and reduce Cd translocation in the Cd-tolerant variety, although it can absorb more Cd. This study provides a foundation for exploring molecular mechanisms of Cd tolerance and transport in broomcorn millet and new insights into improving Cd phytoremediation with this crop through genetic engineering.

A promising crop for cadmium-contamination remediation: Broomcorn millet.

Cadmium (Cd) pollution highly threatens food security and human health, and phytoremediation with Cd-tolerant plants is a cost-effective in situ method for remediation of Cd contamination. Broomcorn millet is known for its strong abiotic stress resistance and can be used as a pioneer crop in both marginal regions and newly reclaimed land. To evaluate their potential in remediation of Cd contamination, a total of 288 broomcorn millet core collections were investigated under hydroponic conditions to compare their capabilities in Cd tolerance, translocation, and accumulation. The core collections varied considerably in their growth parameters, Cd concentration, Cd translocation factor, Cd bioaccumulation factor, and Cd accumulation under Cd stress. According to the Cd tolerance index (TI) values, 160 varieties were Cd tolerant. The Cd TI was significantly positively correlated with Cd accumulation, and the shoot Cd concentrations of five Cd-tolerant varieties were more than 100 mgkg-1, the threshold for being Cd hyperaccumulators. Moreover, the concentrations of essential metal elements were significantly decreased in shoots, and Cd concentration had a significantly positive relationship with magnesium (Mg) and zinc (Zn) concentrations in roots under Cd stress. These results demonstrate that broomcorn millet shows considerable tolerance to Cd stress and great differences in Cd accumulation abilities among varieties. Accordingly, broomcorn millet is a promising plant species for Cd bioremediation, with valuable varieties that have been identified for further study on Cd tolerance mechanisms and the remediation of Cd contamination.

How Does the Waterlogging Regime Affect Crop Yield? A Global Meta-Analysis.

Waterlogging, an abiotic stress, severely restricts crop yield in various parts of the world. Thus, we conducted a meta-analysis of 2,419 comparisons from 115 studies to comprehensively evaluate the overall change in crop yield induced by waterlogging in the global region. The results suggested that waterlogging obviously decreased crop yield by 32.9% on average, compared with no waterlogging, which was a result of a reduced 1,000-grain weight (13.67%), biomass (28.89%), plant height (10.68%), net photosynthetic rate (P n , 39.04%), and leaf area index (LAI, 22.89%). The overall effect of a waterlogging regime on crop yield is related to the crop type; the crop yield reduction varied between wheat (25.53%) and cotton (59.95%), with an overall average value of 36.81% under field conditions. In addition, we also found that compared with no waterlogging, waterlogging in the reproductive growth stage (41.90%) caused a greater yield reduction than in the vegetative growth stage (34.75%). Furthermore, decreases in crop yield were observed with an extension in the waterlogging duration; the greatest decreases in crop yield occurred at 15 < D ≤ 28 (53.19 and 55.96%) under field and potted conditions, respectively. Overall, the results of this meta-analysis showed that waterlogging can decrease crop yield and was mainly affected by crop type, growth stage, and experimental duration.

Xp11.22 duplications in four unrelated Chinese families: delineating the genotype-phenotype relationship for HSD17B10 and FGD1.

BACKGROUND: Xp11.22 duplications have been reported to contribute to nonsyndromic intellectual disability (ID). The HUWE1 gene has been identified in all male Xp11.22 duplication patients and is associated with nonsyndromic ID. Currently, few Xp11.22 duplication cases have been reported in the Chinese population, with limited knowledge regarding the role of other genes in this interval. CASE PRESENTATION: We investigated four unrelated Chinese male Xp11.22 duplication patients, performed a comprehensive clinical evaluation for the patients and discussed the role of other genes in this interval. All patients presented with similar clinical features, including ID, speech impairments and motor delay, which were mostly consistent with those of the Xp11.22 duplication described previously. We searched and compared all cases and noted that one of the probands (Family 1) and DECIPHER case 263,219, who carried small overlapping duplications at Xp11.22 that only covered the entire HSD17B10 gene, also suffered from ID, suggesting the important role of HSD17B10 in this interval. Furthermore, three patients (two probands in Families 3 and 4 and DECIPHER case 249,490) had strikingly similar hypogonadism phenotypes, including micropenis, small testes and cryptorchidism, which have not been previously described in Xp11.22 duplication patients. Interestingly, the FGD1 gene was duplicated only in these three patients. Sufficient evidence has suggested that haploinsufficiency of the FGD1 gene causes Aarskog-Scott syndrome, which is characterized by hypogonadism and other abnormalities. Given that, we are the first group to propose that FGD1 may be a potential dosage-sensitive gene responsible for the hypogonadism observed in our patients. CONCLUSION: We reported novel genotypes and phenotypes in Chinese male Xp11.22 duplication patients, and the HSD17B10 and FGD1 genes may be involved.

[Identification of a de novo MAP2K1 gene variant in an affected patient with Cardio-facio-cutaneous syndrome].

OBJECTIVE: To explore the genotype-phenotype correlation of Cardio-facio-cutaneous syndrome (CFCS) caused by MAP2K1 gene variants. METHODS: Genomic DNA was extracted from peripheral blood sample from a child patient and his parents. Whole exome sequencing (WES) was carried out for the patient. Suspected variant was verified by Sanger sequencing. RESULTS: The patient was a 1-year-8-month old Chinese male who manifested short stature, psychomotor retardation, relative macrocephaly, distinctive facial features, and congenital heart disease. WES test revealed a heterozygous missense c.389A>G (p.Tyr130Cys) variant in the MAP2K1 gene. Sanger sequencing has confirmed the variant as de novo. According to ACMG/AMP guidelines, the variant was classified as pathogenic. CONCLUSION: Compared with previously reported CFCS cases due to MAP2K1 variants. The patient showed obvious behavioral problems, good appetite and tricuspid regurgitation, which may to be novel features for CFCS.

Wnt/ß-Catenin, Carbohydrate Metabolism, and PI3K-Akt Signaling Pathway-Related Genes as Potential Cancer Predictors.

Predicting the outcome after a cancer diagnosis is critical. Advances in high-throughput sequencing technologies provide physicians with vast amounts of data, yet prognostication remains challenging because the data are greatly dimensional and complex. We evaluated Wnt/ß-catenin, carbohydrate metabolism, and PI3K-Akt signaling pathway-related genes as predictive features for classifying tumors and normal samples. Using differentially expressed genes as controls, these pathway-related genes were assessed for accuracy using support-vector machines and three other recommended machine learning models, namely, the random forest, decision tree, and k-nearest neighbor algorithms. The first two outperformed the others. All candidate pathway-related genes yielded areas under the curve exceeding 95.00% for cancer outcomes, and they were most accurate in predicting colorectal cancer. These results suggest that these pathway-related genes are useful and accurate biomarkers for understanding the mechanisms behind cancer development.

No significant association between immunosuppression in solid organ transplantation and prostate cancer risk: a meta-analysis of cohort studies.

BACKGROUND: It is known that organ transplant recipients have a significantly higher risk for developing cancers, but the association between immunosuppression in organ transplantation and the risk for prostate cancer (PCa) remains unclear. We aimed to assess the evidence regarding the association of solid organ transplantation with PCa risk. METHODS: A literature search of the PubMed, Embase, and Web of Science databases was performed up to March 2019. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using a fixed-effect or random-effect model. RESULTS: In total, 26 articles including 33 independent population-based cohort studies with 556,812 recipients and 2,438 PCa cases were identified and included in this meta-analysis. PCa risk in the solid organ transplant recipients did not increase compared with the general population (RR=1.04; 95% CI: 0.90-1.18). Independent analysis of different kinds of organ replacements further indicated immune inhibition in the transplantation of kidney, liver, heart, and lung, and was not associated with elevated PCa risk (RR=0.89; 95% CI: 0.83-0.95; RR=0.61, 95% CI: 0.21-1.02; RR=1.70, 95% CI: 0.88-2.52; RR=0.87, 95% CI: 0.57-1.16, respectively). CONCLUSIONS: This study demonstrated that immunosuppression in solid organ transplant recipients was not associated with higher PCa risk.

Association of smoking status with prognosis in bladder cancer: A meta-analysis.

There is considerable controversy regarding the association between smoking and prognosis in surgically treated bladder cancer. The present meta-analysis was performed to quantify the role of smoking status in bladder cancer recurrence, progression and patient survival by pooling the available previous data. Pubmed, Embase and the Cochrane Library databases were searched for eligible studies published prior to April 2016. Random and fixed effects models were used to calculate the summary relative risk estimates (SRRE). A total of 10,192 patients from 15 studies were included in the meta-analysis. There was evidence of positive associations between current smoking and the risk of recurrence (SRRE=1.23; 95% CI, 1.05-1.45) and mortality (SRRE=1.28; 95% CI, 1.07-1.52) in bladder cancer. Furthermore, former smoking had positive associations with bladder cancer recurrence (SRRE=1.22; 95% CI, 1.09-1.37) and mortality (SRRE=1.20; 95% CI, 1.03-1.41). However, there was no significant association between bladder cancer progression risk and current (SRRE=1.11; 95% CI, 0.71-1.75) or previous smoking (SRRE=1.16; 95% CI, 0.92-1.46). The findings indicate that current and former smoking increase the risk of recurrence and mortality in patients with bladder cancer. However, due to the nonrandomized and retrospective nature of the current study, patients may be prone to potential selection bias. Prospective and larger epidemiological studies with a longer follow-up are required to confirm these findings.

A greater number of dissected lymph nodes is associated with more favorable outcomes in bladder cancer treated by radical cystectomy: a meta-analysis.

The optimal extent of lymph node dissection (LND) is currently not established, and the debate regarding the association between the number of dissected nodes and the outcomes of bladder cancer treated by radical cystectomy (RC) is still ongoing. Therefore, the present meta-analysis was performed to clarify this potential relationship. Eligible studies were retrieved via an electronic search for studies published up to April 2016, and by manual review of the references. A total of 25 cohort studies involving 41,400 bladder cancer patients who underwent RC were included. The summary relative risk estimates (SRRE) based on the highest compared with the lowest categories of LND were estimated by variance-based meta-analysis. Heterogeneity among the study results was explored through stratified analyses. Overall, bladder cancer patients with the highest category of LND had 28%, 34% and 36% reduced risks, corresponding to overall survival (SRRE = 0.72; 95% CI, 0.64-0.80), cancer-specific survival (SRRE = 0.66; 95% CI, 0.54-0.80) and recurrence-free survival (SRRE = 0.64; 95% CI, 0.50-0.82), respectively, compared with patients with the lowest category of LND. In summary, the patients with a greater number of dissected lymph nodes had statistically significant survival advantages in terms of the outcomes of bladder cancer following RC. The number of dissected lymph nodes could be an independent prognostic factor for bladder cancer. These findings need to be validated in prospective and larger epidemiological studies with a longer follow-up period.

The increased excretion of urinary orosomucoid 1 as a useful biomarker for bladder cancer.

Improving the early detection rate and prediction of bladder cancer remains a great challenge in management of this disease. To examine the value of urinary orosomucoid 1 (ORM1) for the early detection and surveillance of bladder cancer, two-dimensional differential gel electrophoresis (2-DE) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOFMS) were applied to identify the differently expressed proteins in urine between bladder cancer and healthy controls. Thirteen different proteins including ORM1 were identified. After verification by western blotting, the ORM1 expressions were quantified in 186 urine samples by enzyme-linked immunosorbent assay (ELISA) correcting for creatinine expression. ELISA quantification showed the urinary ORM1-Cr was found to be higher in bladder cancer patients compared to controls and benign cases (7172.23±3049.67 versus 2243.16±969.01, 2493.48±830.37 ng/ml, respectively, P<0.0001). Furthermore, the pearson correlation analysis indicated that urinary ORM1 had high positive correlation with the pathology classification of bladder cancer. Receiver operating characteristic (ROC) analysis was used to calculate the cut-off value for early diagnosis of bladder cancer, and rendered an optimum cut-off value of 3912.97 ng/mg corresponding to 91.96% sensitivity and 94.34% specificity. Moreover, a cut-off value with 7351.28 ng/mg was utilized to distinguish infiltrating urothelial carcinoma from bladder cancer patients corresponding to 91.89% sensitivity and 90.67% specificity. In conclusion, our findings suggested the elevated urinary ORM1 could be a useful biomarker for bladder cancer. Further research is warranted to elucidate the pathogenic mechanisms of elevated ORM1.

[Value of suprapubic cystostomy in bipolar transurethral resection of the prostate for benign prostatic hyperplasia below 80 gram].

OBJECTIVE: To investigate the perioperative benefit of suprapubic cystostomy in bipolar transurethral resection of the prostate (B-TURP) for treatment of benign prostatic hyperplasia (BPH) below 80 g. METHODS: This retrospective study was conducted in patients undergoing B-TURP for BPH below 80 g, who were stratified with respect of suprapubic cystostomy in B-TURP. The end points including the safety, efficiency, complications and nursing care were compared between the two groups. RESULTS: A total of 585 patients were enrolled, including 366 in cystostomy group and 219 in non-cystostomy group. The two groups showed similar postoperative reduction of serum sodium (0.06 vs 0.54 mmol/L, P>0.05), hematocrict (2.44% vs 2.89%, P>0.05), and blood hemoglobin concentration (9.62 vs 10.42 g/L, P>0.05), with comparable weight of resected prostate (42.50 vs 43.76 g, P>0.05). The operation time was significantly longer in cystostomy group than in non-cystostomy group (90.75 vs 76.28 min, P<0.05), but the rate of blood transfusion and incidences of postoperative fever and catheter blocking were comparable between the two groups. Compared with the non-cystostomy group, cystostomy group had significantly longer time for bladder washing (3.15 vs 2.57 days, P<0.05), catheter indwelling time (5.19 vs 4.15 days, P<0.05), and hospital stay after the operation (7.36 vs 5.65 days, P<0.05). CONCLUSIONS: In B-TURP for BPH below the weight of 80 g, suprapubic cystostomy is associated with a longer time for operation, bladder washing, catheter indwelling and postoperative hospital stay, and thus provides no obvious benefits for the patients.

[Vasectomy does not increase the risk of prostate cancer in Chinese men: A meta-analysis].

OBJECTIVE: To investigate the correlation of vasectomy with the risk of prostate cancer in Chinese men. METHODS: We systematically searched the databases CNKI, VIP, Wanfang, PubMed, Embase, and Cochrane Library for the literature relating the relationship between vasectomy and the risk of prostate cancer in Chinese males up to December 2014. According to the inclusion and exclusion criteria, two investigators independently selected the eligible publications, evaluated their quality, and extracted relevant information, followed by a meta-analysis with the software STATA 12.0. RESULTS: Nine studies were included in the analysis involving 1 202 cases of prostate cancer and 4,496 controls. Random-effect model analysis revealed no statistically significant correlation between vasectomy and the risk of prostate cancer (OR = 1.05; 95% CI 0.62-1.79), with an obvious heterogeneity (P < 0.001, I2 = 85.7%). No significant publication bias was found among the included studies (Egger, P = 0.824; Begg, P = 0.348). CONCLUSION: The results of our meta-analysis do not support the association of vasectomy with the increased risk of prostate cancer in Chinese population.

5-Aza-2'-Deoxycytidine and CDDP Synergistically Induce Apoptosis in Renal Carcinoma Cells via Enhancing the APAF-1 Activity.

BACKGROUND: It has been reported that the hypermethylation of APAF-1, DAPK-1 and other tumor suppressive genes (TSGs) correlates with progression of renal cell carcinoma and exerts prognostic and diagnostic relevance in renal cell carcinoma. A recent study has confirmed that demethylation regulates the TSGs expression and proliferation of various types of cancer cells. The present study was to recognize a potential anti-tumor effect of 5-aza-2'-deoxycytidine (DAC), a demethylation agent. METHODS: We evaluated the DNA demethylation by DAC in human renal carcinoma cells and determined the synergism of the demethylation with the toxicity of Cisplatin (CDDP), which is a commonly utilized anti-tumor agent for renal carcinoma. RESULTS: It was demonstrated that DAC promoted a significant global genomic demethylation and improved APAF-1 expression at both mRNA and protein levels. The DAC treatment deteriorated the CDDP-induced viability decreasing Caki or ACHN cells and synergized the apoptosis induction of CDDP in ACHN cells. The treatment with both DAC and CDDP promoted a significantly higher level of renal carcinoma cell apoptosis than singular DAC or CDDP treatment. The APAF-1 knockdown significantly inhibited the synergism of DAC with the CDDP-induced apoptosis in ACHN cells. CONCLUSIONS: The present study confirmed that DAC demethylated the CpGs, particularly APAF-1 in renal carcinoma cells, and that the demethylation synergized the cytotoxity of CDDP in renal carcinoma cells via enhancing the CDDP-induced apoptosis.

Associations of dietary patterns with the risk of all-cause, CVD and stroke mortality: a meta-analysis of prospective cohort studies.

Considerable controversy exists regarding the associations of dietary patterns with the risk of all-cause, CVD and stroke mortality. Therefore, a meta-analysis was conducted to elucidate the potential associations between dietary patterns and the risk of all-cause, CVD and stroke mortality. The PubMed database was searched for prospective cohort studies on the associations between dietary patterns and the risk of all-cause, CVD and stroke mortality published until February 2014. Random-effects models were used to calculate the summary relative risk estimates (SRRE) based on the highest v. the lowest category of dietary pattern scores. Stratified analyses were conducted based on sex, geographical region, follow-up duration, and adjustment/non-adjustment for energy intake. A total of thirteen prospective cohort studies involving 338 787 participants were included in the meta-analysis. There was evidence of inverse associations between the prudent/healthy dietary pattern and the risk of all-cause (SRRE = 0·76, 95% CI 0·68, 0·86) and CVD (SRRE = 0·81, 95% CI 0·75, 0·87) mortality and an absence of association between this dietary pattern and stroke mortality (SRRE = 0·89, 95% CI 0·77, 1·02). However, no significant associations were observed between the Western/unhealthy dietary pattern and the risk of all-cause (SRRE = 1·07, 95% CI 0·96, 1·20), CVD (SRRE = 0·99, 95% CI 0·91, 1·08) and stroke (SRRE = 0·94, 95% CI 0·81, 1·10) mortality. In conclusion, the findings provide evidence that greater adherence to a prudent/healthy dietary pattern is associated with a lower risk of all-cause and CVD mortality and not significantly associated with stroke mortality and that the Western/unhealthy dietary pattern is not associated with all-cause, CVD and stroke mortality. Further studies are required to confirm these findings.

Red and processed meat intake and risk of bladder cancer: a meta-analysis.

Findings from epidemiologic studies concerning red and processed meat intake and bladder cancer risk remain conflicting. Thus, we conducted this meta-analysis to examine the associations of red and processed meat intake with bladder cancer. Eligible studies published up to May 2014 were retrieved via both computer searches and review of references. Finally, we identified 14 studies on red meat (involving 9,084 cases) and 11 studies on processed meat (7,562 cases) involving up to 1,558,848 individuals. Random-effects models were used to estimate summary relative risk estimates (SRRE) based on high vs. low intake, and heterogeneity between study results was explored through stratified analyses on the basis of red/processed meat category, gender, study design and geographical region. Overall, the SRRE for all studies regarding red meat intake was 1.15 (95% CI: 0.97-1.36). Significant positive association was observed between processed meat consumption and bladder cancer (SRRE = 1.22; 95% CI: 1.04-1.43). Interestingly, increased by 25% and 33% risk of bladder cancer were observed for red meat and processed meat intake respectively in populations from the American continent. In conclusion, our fi ndings showed that there was an absence of an association between red meat intake and bladder cancer, but suggested that high consumption of processed meat probably correlated with rising risk of bladder cancer. In addition, positive relationships were observed regarding people intake of red and processed meat in the American continent. These findings need to be confirmed in future research.

Norcantharidin inhibits DNA replication and induces mitotic catastrophe by degrading initiation protein Cdc6.

Cdc6, an essential initiation protein for DNA replication, also participates in the ATR checkpoint pathway and plays a vital role in tumorigenesis. It is involved in the androgen receptor (AR) signal transduction and promotes the malignant progression of prostate cancer (PCa). In this study, we report that norcantharidin (NCTD) induces the degradation of Cdc6 in DU145 PCa cells and as a result, the assembly of pre-replication complexes (pre-RCs) was disturbed and DNA replication was inhibited. Furthermore, treatment with NCTD blocked ATR binding to chromatin and the cells progressed into mitosis under stress induced by hydroxyurea (HU), indicating that the ATR checkpoint was evaded. Aberrant mitosis and hence, apoptosis were also observed following treatment with NCTD. Finally, NCTD exerted strong synergistic cytotoxic effects in combination with another mitotic inhibitor, paclitaxel, [combination index (CI <1)]. These data suggest that NCTD not only inhibits DNA replication but also disables the ATR-dependent checkpoint pathway by inducing Cdc6 degradation, which leads to mitotic catastrophe in DU145 cells. These findings also provide a promising prospect for the combination treatment of paclitaxel and NCTD or Cdc6 deletion in PCa.