Sharply and simultaneously increasing pollutant accumulations in cells of organisms induced by rare earth elements in the environment of Nanjing.

Exploring the factors that simultaneously increase the accumulation of various pollutants in cells of organisms to restrict the toxic effects of pollutants on organisms has become a focus of research aimed at protecting ecosystems. Here, we found that the accumulation of organic [e.g., benzo(a)pyrene (BaP)], inorganic [e.g., cadmium (Cd)] and emerging [e.g., rare earth elements (REEs)] pollutants in leaf cells of different plants grown in Nanjing was 567-1022%, 547-922% and 972-1392% of those grown in Haikou, respectively, when the concentration of REEs in rainwater of Nanjing and Haikou was 4.31 × 10-3 µg/L and 3.04 × 10-6 µg/L. Unprecedentedly, endocytosis in leaf cells of different plants grown in Nanjing was activated by REEs, and then extracellular BaP, Cd and REEs (e.g. terbium) were transported into these leaf cells together via endocytic vesicles. Particularly, the co-accumulation of those pollutants in these leaf cells was sharply increased, thus magnifying their toxic effects on these plants. Furthermore, the co-accumulation of those pollutants in human cells was also significantly increased by REEs, in a similar way to these leaf cells. Therefore, REEs in environments are key factors that greatly increase the co-accumulation of various pollutants in cells of organisms. These results provide new insights into how pollutants are accumulated in cells of organisms in ecosystems, informing a reference for making policy to ensure the safety of ecosystems.

Nomograms to Predict Overall and Cancer-Specific Survival in Gastric Signet-Ring Cell Carcinoma.

BACKGROUND: The objective of our study was to develop and validate nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with signet-ring cell carcinoma (SRCC) of the stomach. METHODS: Data were collected from the Surveillance, Epidemiology, and End Results (SEER) database. A total of 1781 patients were randomly allocated to a training set (n = 1335) and a validation set (n = 446). Univariate and multivariate analyses were used to determine the prognostic effect of variables. Nomograms were developed to estimate OS and CSS and assessed using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC), and decision curve analyses (DCA). DCA was utilized to compare the nomograms and the Tumor-Node-Metastasis (TNM) staging system. RESULTS: Age, race, tumor size, T, N, M stage, and use of surgery and/or radiotherapy were included in the nomograms. C-indexes for OS and CSS were 0.74 and 0.75 in the training set, respectively. C-indexes for OS and CSS were 0.76 and 0.76 in the validation set. Calibration plots and receiver operating characteristic (ROC) curves showed good predictive accuracy. According to the decision curve analyses (DCA), the new model was more useful than the TNM staging system. CONCLUSIONS: We developed nomograms to predict OS and CSS in patients with SRCC of the stomach. Nomograms may be a valuable clinical supplement of the conventional TNM staging system.

CgNPG1 as a Novel Pathogenic Gene of Colletotrichum gloeosporioides From Hevea brasiliensis in Mycelial Growth, Conidiation, and the Invasive Structures Development.

The rubber tree (Hevea brasiliensis) is a tropical perennial crop for the primary source of natural rubber. Colletotrichum gloeosporioides from Hevea brasiliensis (C. gloeosporioides Hb) and Colletotrichum acutatum from Hevea brasiliensis (C. acutatum Hb) are the causal agents of rubber tree anthracnose and lead to serious loss of natural rubber production. Inoculation tests showed that C. gloeosporioides Hb possessed higher pathogenicity than C. acutatum Hb to the rubber tree. Genomic analysis revealed that an unknown gene, named CgNPG1 (a Novel Pathogenic Gene 1), was presented in the genome of C. gloeosporioides Hb but not identified in C. acutatum Hb. CgNPG1 was predicted to encode a small secretory protein without any conserved domain. To investigate the functions of CgNPG1 in C. gloeosporioides Hb and in C. acutatum Hb, the gene deletion and overexpression mutants were generated. The phenotype analysis showed that deletion of CgNPG1 led to changed conidia morphology, decreased mycelial growth, conidiation, conidia germination rate, appressorium formation rate, and pathogenicity of C. gloeosporioides Hb to the rubber tree. Meanwhile, heterogeneous expression of CgNPG1 in C. acutatum Hb significantly changed the conidia morphology and improved the mycelial growth rate, conidiation, conidia germination rate, appressorium formation rate, and the pathogenicity of C. acutatum Hb to the rubber tree. Consistently, CgNPG1 increased the expression level of CaCRZ1 and CaCMK1 in C. acutatum Hb. These data suggested that CgNPG1 contributed to mycelial growth, conidiation, the development of invasive structures, and the pathogenicity of Colletotrichum to the rubber tree, which might be related to the modulation of CaCRZ1 and mitogen-activated protein kinase CMK1. Our results provided new insight into CgNPG1 in regulating growth and pathogenicity of the Colletotrichum spp.

Heat shock protein 90 co-chaperone modules fine-tune the antagonistic interaction between salicylic acid and auxin biosynthesis in cassava.

Heat shock protein 90 (HSP90) is an important molecular chaperone in plants. However, HSP90-mediated plant immune response remains elusive in cassava. In this study, cassava bacterial blight (CBB) induces the expression of MeHsf8, which directly targets MeHSP90.9 to activate its expression and immune response. Further identification of SHI-related sequence 1 (MeSRS1) and MeWRKY20 as MeHSP90.9 co-chaperones revealed the underlying mechanism of MeHSP90.9-mediated immune response. MeHSP90.9 interacts with MeSRS1 and MeWRKY20 to promote their transcriptional activation of salicylic acid (SA) biosynthetic gene avrPphB Susceptible 3 (MePBS3) and tryptophan metabolic gene N-acetylserotonin O-methyltransferase 2 (MeASMT2), respectively, so as to activate SA biosynthesis but inhibit tryptophan-derived auxin biosynthesis. Notably, genetic experiments confirmed that overexpressing MePBS3 and MeASMT2 could rescue the effects of silencing MeHsf8-MeHSP90.9 on disease resistance. This study highlights the dual regulation of SA and auxin biosynthesis by MeHSP90.9, providing the mechanistic understanding of MeHSP90.9 client partners in plant immunity.

Zinc finger of Arabidopsis thaliana 6 is involved in melatonin-mediated auxin signaling through interacting INDETERMINATE DOMAIN15 and INDOLE-3-ACETIC ACID 17.

Although accumulating evidence demonstrates the cross talk between melatonin and auxin as derivatives of tryptophan, the underlying signaling events remain unclear. In this study, we found that melatonin and auxin mediated the transcriptional levels of zinc finger of Arabidopsis thaliana (ZAT6) in a mutually antagonistic manner. ZAT6 negatively modulated the endogenous auxin level, and ZAT6 knockdown plants were less sensitive to melatonin-regulated auxin biosynthesis, indicating its involvement in melatonin-mediated auxin accumulation. Additionally, the identification of INDETERMINATE DOMAIN15 (IDD15) and INDOLE-3-ACETIC ACID 17 (IAA17) in Arabidopsis that interacted with ZAT6 in vivo provided new insight of ZAT6-mediated auxin signaling. Further investigation showed that ZAT6 repressed the transcription activation of IDD15 on the YUC2 promoter, while ZAT6 inhibited the interaction of TRANSPORT INHIBITOR RESPONSE 1 (TIR1) and IAA17 through competitively binding to IAA17. Thus, both auxin synthesis and the auxin response were negatively modulated by ZAT6. Taken together, ZAT6 is involved in melatonin-mediated auxin signaling through forming an interacting complex of auxin signaling pathway in Arabidopsis.

Molecular identification of GAPDHs in cassava highlights the antagonism of MeGAPCs and MeATG8s in plant disease resistance against cassava bacterial blight.

KEY MESSAGE: MeGAPCs were identified as negative regulators of plant disease resistance, and the interaction of MeGAPCs and MeATG8s was highlighted in plant defense response. As an important enzyme of glycolysis metabolic pathway, glyceraldehyde-3-P dehydrogenase (GAPDH) plays important roles in plant development, abiotic stress and immune responses. Cassava (Manihot esculenta) is most important tropical crop and one of the major food crops, however, no information is available about GAPDH gene family in cassava. In this study, 14 MeGAPDHs including 6 cytosol GAPDHs (MeGAPCs) were identified from cassava, and the transcripts of 14 MeGAPDHs in response to Xanthomonas axonopodis pv manihotis (Xam) indicated their possible involvement in immune responses. Further investigation showed that MeGAPCs are negative regulators of disease resistance against Xam. Through transient expression in Nicotiana benthamiana, we found that overexpression of MeGAPCs led to decreased disease resistance against Xam. On the contrary, MeGAPCs-silenced cassava plants through virus-induced gene silencing (VIGS) conferred improved disease resistance. Notably, MeGAPCs physically interacted with autophagy-related protein 8b (MeATG8b) and MeATG8e and inhibited autophagic activity. Moreover, MeATG8b and MeATG8e negatively regulated the activities of NAD-dependent MeGAPDHs, and are involved in MeGAPCs-mediated disease resistance. Taken together, this study highlights the involvement of MeGAPCs in plant disease resistance, through interacting with MeATG8b and MeATG8e.

Melatonin biosynthesis enzymes recruit WRKY transcription factors to regulate melatonin accumulation and transcriptional activity on W-box in cassava.

Melatonin is widely involved in growth, development, and stress responses in plants. Although the melatonin synthesis enzymes have been identified in various plants, their interacting proteins remain unknown. Herein, overexpression of tryptophan decarboxylase 2 (MeTDC2)-interacting proteins, N-acetylserotonin O-methyltransferase 2 (MeASMT2) interacting proteins, and N-acetylserotonin O-methyltransferase 3 (MeASMT3) in cassava leaf protoplasts resulted in more melatonin than when other enzymes were overexpressed. Through yeast two-hybrid, 14 MeTDC2-interacting proteins, 24 MeASMT2 interacting proteins, and 9 MeASMT3-interacting proteins were identified. Notably, we highlighted MeWRKY20 and MeWRKY75 as common interacting proteins of the 3 enzymes, as evidenced by yeast two-hybrid, and in vivo bimolecular fluorescence complementation (BiFC). Moreover, co-overexpression of MeTDC2/MeASMT2/3 with MeWRKY20/75 in cassava leaf protoplasts did not only activated the transcriptional activities of MeWRKY20 and MeWRKY75 on W-box, but also induced the effects of MeTDC2, MeASMT2/3 on endogenous melatonin levels. Taken together, 3 melatonin synthesis enzymes (MeTDC2, MeASMT2/3) interact with MeWRKY20/75 to form a protein complex in cassava. This information significantly extends the knowledge of the complex modulation of plant melatonin signaling.

Overexpressing OsMAPK12-1 inhibits plant growth and enhances resistance to bacterial disease in rice.

Mitogen-activated protein kinases (MAPKs) play important roles in plant growth and development, plant abiotic stresses signalling pathway and plant-pathogen interactions. However, little is known about the roles of MAPKs in modulating plant growth and pathogen resistance. In this study, we found that OsMAPK12-1, an alternatively spliced form of BWMK1 in rice (Oryza sativa L.), was induced by various elicitors, such as jasmonic acid, salicylic acid, melatonin and bacterial pathogens. To further investigate the involvement of OsMAPK12-1 in plant growth and stress responses to bacterial pathogens, we constructed OsMAPK12-1 overexpression and knockdown (RNAi) transgenic rice lines. Interestingly, overexpressing OsMAP12-1 inhibited seed germination and seedling growth. Additionally, the OsMAP12-1-overexpression lines displayed enhanced disease resistance against Xanthomonas oryzae pv. oryzae PXO99 and Xanthomonas oryzae pv. oryzicola RS105, whereas the OsMAPK12-1-RNAi lines were more susceptible to these pathogens than wild type. These results suggest that OsMAPK12-1 plays a negative role in plant growth and positively modulates disease resistance against bacterial blight and streak in rice.

Nuclear expression and/or reduced membranous expression of ß-catenin correlate with poor prognosis in colorectal carcinoma: A meta-analysis.

BACKGROUND: The differential subcellular localizations of ß-catenin (including membrane, cytoplasm, and nucleus) play different roles in the progression of colorectal cancer (CRC). However, the correlation between each subcellular localization of ß-catenin and the prognosis of CRC patients remains undetermined. METHODS: Systematic strategies were applied to search for eligible published studies in the PubMed, Embase, and Web of Science databases. The correlation between each subcellular localizations of ß-catenin expression and patients' clinicopathological features or prognosis was analyzed. RESULTS: Finally, this meta-analysis, including 6238 cases from 34 studies, revealed that ß-catenin overexpression in the nucleus (HR: 1.50[95% CI: 1.08-2.10]) or reduced expression of ß-catenin in the membrane (HR: 1.33[95% CI: 1.15-1.54]) significantly correlated with lower 5-year overall survival (OS). Conversely, overexpression of ß-catenin in the cytoplasm (HR: 1.00[95% CI: 0.85-1.18]) did not show significant association with 5-year OS. CONCLUSION: This study suggested that ß-catenin overexpression in the nucleus or reduced expression in the membrane, but not its overexpression in cytoplasm, could serve as a valuable prognostic predictor for CRC. However, additional large and well-designed prospective studies are required to verify our results.

Risk prediction and clinical model building for lymph node metastasis in papillary thyroid microcarcinoma.

The surgical management of papillary thyroid microcarcinoma (PTMC), especially regarding the necessity of central/lateral lymph node dissection, remains controversial. This study investigated the clinicopathologic factors predictive of lymph node metastasis (LNM) in patients diagnosed with PTMC. Multivariate logistic regression analysis was used for PTMC patients identified from the Surveillance, Epidemiology, and End Results database who were treated by surgery between 2002 and 2012, to determine the association of clinicopathologic factors with LNM. According to the results, a total of 31,017 patients met the inclusion criteria of the study. Final histology confirmed 2,135 (6.9%) cases of N1a disease and 1,684 cases (5.4%) of N1b disease. Our multivariate logistic regression analysis identified variables associated with both central LNM and lateral lymph node metastasis (LLNM), including a younger age (<45 years), male sex, non-Hispanic white and other race, classical papillary histology, larger tumor size, multifocality, and extrathyroidal extension; distant metastasis was also significantly associated with LLNM. The significant predictors identified from multivariable logistic regression were integrated into a statistical model that showed that extrathyroidal extension had maximum weight in the predictive role for LNM. LLNM was validated to be a significant risk factor for cancer-specific death in Cox regression analyses, whereas central LNM failed to predict a worse cancer-specific survival according to our data. Therefore, we suggested that central lymph node dissection could be performed in certain patients with risk factors. Given the prevalence of LLNM in PTMC, a thorough inspection of the lateral compartment is recommended in PTMC patients with risk factors for precise staging; from the viewpoint of a radical treatment for tumors, prophylactic lateral lymph node dissection that aims to remove the occult lateral lymph nodes may be an option for PTMC with risk factors. Multicenter studies with long-term follow-up are recommended to better understand the risk factors and surgical management for cervical nodes in PTMC.

Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer.

Papillary thyroid cancer (PTC) often presents as multifocal tumor;, however, whether multifocality is associated with poor prognosis remains controversial. The aims of this retrospective study were to identify the characteristics of PTC with multifocal tumors and evaluate the association between the location and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as three groups: N1 (solitary tumor), N2 (2 or more foci within unilateral lobe of thyroid), and N3 (bilateral tumors, at least one tumor focus for each lobe of thyroid). We analyzed the differences of clinicopathologic features and clinical outcomes among the three groups. Cox regression model was used to assess the relation between the different locations of multifocal tumors and prognosis. Although the differences of clinicopathologic features such as the size of tumor, extrathyroidal extension, and cervical lymph node metastasis were not significant among the three groups, the bilateral-multifocality was proved to be an independent risk factor for neck recurrence (hazard ratio (HR) = 4.052, 95 % confidence interval (CI) 2.070-7.933), distant metastasis (HR = 3.860, 95 % CI 1.507-9.884), and cancer death (HR = 7.252, 95 % 2.189-24.025). In addition, extrathyroidal extension (HR = 2.291, 95 % CI 1.185-4.427) and older age >45 years (HR = 6.721, 95 % CI 2.300-19.637) were also significant predictors for neck recurrence and cancer death, respectively. Therefore, bilateral-multifocality as an indicator for more extensive tumor location could be used to assess the risk of recurrence and mortality in PTC. Given the poor prognosis associated with bilateral-multifocality and other risk factors, aggressive therapy and intensive follow-up were recommended for PTC patients with them.

The impact of coexistent Hashimoto's thyroiditis on lymph node metastasis and prognosis in papillary thyroid microcarcinoma.

The impact of coexistent Hashimoto's thyroiditis (HT) on lymph node metastasis (LNM) and prognosis in papillary thyroid microcarcinoma (PTMC) remains controversial. We evaluated the association of coexistent HT with clinicopathologic parameters, LNM, and prognosis by retrospectively reviewing a series of consecutive patients treated for PTMC at Fudan University Cancer Center from January 2005 to December 2010. Of all 1,250 patients with complete data for analysis, 364 (29.1 %) had coexistent HT (HT group) and 886 patients (70.9 %) had no evidence of HT (control group). The HT group had higher proportion of female (87.9 vs 70.1 %) patients, higher mean level of thyroid-stimulating hormone (TSH) (2.39 vs 2.00 mIU/L), and lower incidence of extrathyroidal extension (7.4 vs 11.7 %) than those in the control group. However, the incidence of LNM and recurrence was similar between the two groups, and HT was not associated with LNM and recurrence. A series of clinicopathologic factors identified for predicting LNM and recurrence in the control group did not show any prediction in the HT group. In summary, this study suggested that coexistent HT had insignificant protective effect on LNM and prognosis in PTMC, which was inconsistent with prior studies. Further studies aiming to determine novel predictors are recommended in PTMC patients with coexistent HT.