Deubiquitinase PSMD14 enhances hepatocellular carcinoma growth and metastasis by stabilizing GRB2.

Hepatocellular carcinoma (HCC) has emerged as one of the most common malignancies worldwide. It is associated with a high mortality rate, as evident from its increasing incidence and extremely poor prognosis. The deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) has been reported to act as an oncogene in several human cancers. The present study aimed to reveal the functional significance of PSMD14 in HCC progression and the underlying mechanisms. We found that PSMD14 was significantly upregulated in HCC tissues. Overexpression of PSMD14 correlated with vascular invasion, tumor number, tumor recurrence, and poor tumor-free and overall survival of patients with HCC. Knockdown and overexpression experiments demonstrated that PSMD14 promoted proliferation, migration, and invasion in HCC cells in vitro, and facilitated tumor growth and metastasis in vivo. Mechanistically, we identified PSMD14 as a novel post-translational regulator of GRB2. PSMD14 inhibits degradation of GRB2 via deubiquitinating this oncoprotein in HCC cells. Furthermore, pharmacological inhibition of PSMD14 with O-phenanthroline (OPA) suppressed the malignant behavior of HCC cells in vitro and in vivo. In conclusion, our findings suggest that PSMD14 could serve as a novel promising therapeutic candidate for HCC

Deubiquitinase PSMD14 enhances hepatocellular carcinoma growth and metastasis by stabilizing GRB2

Abstract(#br)Hepatocellular carcinoma (HCC) has emerged as one of the most common malignancies worldwide. It is associated with a high mortality rate, as evident from its increasing incidence and extremely poor prognosis. The deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) has been reported to act as an oncogene in several human cancers. The present study aimed to reveal the functional significance of PSMD14 in HCC progression and the underlying mechanisms. We found that PSMD14 was significantly upregulated in HCC tissues. Overexpression of PSMD14 correlated with vascular invasion, tumor number, tumor recurrence, and poor tumor-free and overall survival of patients with HCC. Knockdown and overexpression experiments demonstrated that PSMD14 promoted proliferation, migration, and invasion in HCC cells in vitro , and facilitated tumor growth and metastasis in vivo . Mechanistically, we identified PSMD14 as a novel post-translational regulator of GRB2. PSMD14 inhibits degradation of GRB2 via deubiquitinating this oncoprotein in HCC cells. Furthermore, pharmacological inhibition of PSMD14 with O-phenanthroline (OPA) suppressed the malignant behavior of HCC cells in vitro and in vivo . In conclusion, our findings suggest that PSMD14 could serve as a novel promising therapeutic candidate for HCC

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Heavy metal characteristics of vegetables and their soils in Foshan City

Investigation of the vegetable garden soil in Foshan City 4 kinds of heavy metals Cu, Pb, Zn and Cd in the total and different forms of content, while also investigating a variety of vegetables and edible part of the Cd content. The results show that, Foshan City, the heavy metal content in vegetable field exceed the national and the background value of Guangdong Province, the pollution index to the maximum Cd, Cu, followed by, Cd elements of the highest validity coefficients. Foshan City, edible part of vegetables found excessive Cd, leafy soil Cd content and Cd the full amount of exchangeable manganese content and the amount of state showed a significant positive correlation. The state of heavy metal content of vegetable soil in Foshan city was investigated. The total content and available content of 4 heavy metal elements (Cd, Pb, Zn, and Cu) were analyzed and measured. The result indicated that the heavy metal content of vegetable soil in Foshan city was greater than the average in other areas throughout Guangdong Province or even the whole country. The valid coefficient of Cd element was the greatest. The content of Cd in vegetables was greater than the state vegetable sanitation standard. In different kinds of vegetables, the content of Cd in leaf-vegetable had very significant correlation with the content of different sort Cd in soil. which indicated that the content of Cd in vegetables was affected by the content of Cd in soil

Sediment nitrogen cycling rates and microbial abundance along a submerged vegetation gradient in a eutrophic lake

Decline of submerged vegetation is one of the most serious ecological problems in eutrophic lakes worldwide. Although restoration of submerged vegetation is widely assumed to enhance ecological functions (e.g., nitrogen removal) and aquatic biodiversity, the evidence for this assumption is very limited. Here, we investigated the spatio-temporal patterns of sediment potential nitrification, unamended denitrification and N(2)Oproduction rates along a vegetation gradient in the Lake Honghu, where submerged vegetation was largely restored by prohibiting net-pen aquaculture. We also used five functional genes as markers to quantify the abundance of sediment nitrifying and denitrifying microorganisms. Results showed that unvegetated sediments supported greater nitrification rates than rhizosphere sediments of perennial or seasonal vegetation. However, the absence of submerged vegetation had no significant effect on denitrification and N2O production rates. Additionally, the abundance of functional microorganisms in sediments was not significantly different among vegetation types. Season had a strong effect on both nitrogen cycling processes and microbial abundances. The highest nitrification rates were observed in September, while the highest denitrification rates occurred in December. The temporal variation of sediment nitrification, denitrification and N2O production rates could be due to changes in water quality and sediment properties rather than submerged vegetation and microbial abundances. Our findings highlight that vegetation restoration in eutrophic lakes improves water quality but does not enhance sediment nitrogen removal rates and microbial abundances. Therefore, for reducing the N level in eutrophic lakes, major efforts should be made to control nutrients export from terrestrial ecosystems. (c) 2017 Elsevier B.V. All rights reserved

Environmental factors, but not abundance and diversity of nitrifying microorganisms, explain sediment nitrification rates in Yangtze lakes

Sediment nitrification plays a vital role in nitrogen (N) biogeochemical cycling and ecological function of an aquatic ecosystem. The relative importance of environmental factors and nitrifying microbial communities in regulating sediment nitrification process has received less attention, especially in aquatic habitats where high N loads are frequently detected. Here, we report the potential nitrification rates of 35 sediment samples from 10 shallow lakes in the Yangtze River basin. The diversity and abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB) were quantified using archaeal and bacterial amoA genes. The results showed that there was no significant difference in sediment nitrification rates among sites of different trophic state. The nitrification rates were positively related to water chlorophyll-a, sediment N and carbon levels, but not significantly associated with diversity and abundance of ammonia-oxidizing microorganisms and submerged plants. Interestingly, the abundance and diversity of sediment AOB but not AOA communities were significantly influenced by trophic state. In addition, AOB communities were more sensitive to changes in local environments and catchment land uses than the AOA communities. Using path analysis, we found that 55-60% of the indirect effect of catchment land uses on nitrification rates was mediated via sediment N content. Our findings suggest that, although nitrification is a microbial process, variation in sediment nitrification rates in Yangtze lakes is mainly explained by abiotic factors but not by microbial abundance and diversity

Functional Role of p53 in the Regulation of Chemical-Induced Oxidative Stress

The nuclear transcription factor p53, discovered in 1979, has a broad range of biological functions, primarily the regulation of apoptosis, the cell cycle, and DNA repair. In addition to these canonical functions, a growing body of evidence suggests that p53 plays an important role in regulating intracellular redox homeostasis through transcriptional and nontranscriptional mechanisms. Oxidative stress induction and p53 activation are common responses to chemical exposure and are suggested to play critical roles in chemical-induced toxicity. The activation of p53 can exert either prooxidant or antioxidant activity, depending on the context. In this review, we discuss the functional role of p53 in regulating chemical-induced oxidative stress, summarize the potential signaling pathways involved in p53’s regulation of chemically mediated oxidative stress, and propose issues that should be addressed in future studies to improve understanding of the relationship between p53 and chemical-induced oxidative stress

Evaluation of ITS2 for intraspecific identification of Paeonia lactiflora cultivars

Herbaceous peony (Paeonia lactiflora Pall.) is an important ornamental and medicinal plant. DNA barcodes can reveal species identity via the nucleotide diversity of short DNA segments. In this study, two main candidate DNA barcodes (ITS2 and psbA-trnH) were tested to identify twenty-one cutting cultivars of P. lactiflora and their wild species. The efficacy of the candidate DNA barcodes was assessed by PCR amplification, sequence quality, sequence diversity, rate of correct identification, and phylogenetic analysis. ITS2 was easy to be amplified and sequenced among the samples. The identification by Blastn and phylogenetic analysis was 95.4% and 63.6%, respectively. For psbA-trnH, the presence of poly A-T led to sequencing failure which limited its use as DNA barcode candidate. Moreover, the authentic efficiency of psbA-trnH was lower than ITS2. The results showed that ITS2 is suitable as a candidate DNA barcode for the intraspecific identification of P. lactiflora cultivars

Isolation, Purification, and Antioxidant Activities of Polysaccharides from Choerospondias axillaris Leaves

The extraction, characterization and antioxidant activity of polysaccharides from Choerospondias axillaris leaves were investigated in the present study. Two purified polysaccharide fractions, CALP-1 and CALP-2, were isolated from crude Choerospondias axillaris leaf polysaccharides (CALP) by DEAE-52 cellulose chromatography and Sephadex G-100 column chromatography. The characteristics of CAL-1 and CALP-2 were determined by using High-performance Gel Permeation Chromatography (HPGPC), High-Performance Anion-Exchange Chromatography, HPAEC (HPAEC-PAD) and Fourier transform infrared spectroscopy (FTIR). CALP-1 with molecular weight of 11.20 KDa was comprised of Rhamnose, Arabinose, Galactose, Glucose, Xylose, Mannose and galacturonic acid in a molar ratio of 5.16:2.31:5.50:27.18:1.00:0.76:1.07. CAL-2 with molecular weight of 8.03 KDa consisted of Rhamnose, Arabinose, Galactose, Glucose, and galacturonic acid at a ratio of 1.38:3.63:18.84:8.28:1.45. FTIR revealed that CALP-1 and CALP-2 were acidic polysaccharides. The antioxidant activity of crude CALP, CALP-1 and CALP-2 was evaluated in vitro. The fraction CALP-2 was demonstrated to be of polysaccharide nature containing a large percentage of Galactose but no Xylose and Mannose. The antioxidant activity assays showed that CALP-1 and CALP-2 exhibited antioxidant and scavenging activities on hydroxyl and DPPH radicals in vitro. Compared with pure polysaccharide, crude CALP exhibited stronger anti-oxidant activities. These results will provide a better understanding of Choerospondias axillaris leaf polysaccharide and promote the potential applications of Choerospondias axillaris leaf polysaccharide in the pharmacological field and as a natural antioxidant