Tailoring the density of states of Ni(OH)2 with Ni0 towards solar urea wastewater splitting.

Solar urea wastewater splitting is capable of producing hydrogen and degrading the urea pollutant simultaneously. Nickel hydroxide (Ni(OH)2) has been recognized as an effective cocatalyst for the urea oxidation reaction (UOR). But the lack of an efficient preparation method and a suitable Ni(OH)2 based cocatalyst limits the performances of solar urea wastewater splitting. Herein, a potential-cycling method is developed with a high-purity nickel plate serving as the counter electrode and nickel source in a three-electrode configuration. Spherical Ni0-doped Ni(OH)2 nanoparticles are successfully synthesized on the surface of TiO2 nanorod arrays. The photocurrent density of TiO2/Ni0:Ni(OH)2 can reach 0.56 mA cm-2 at 1.23 VRHE in 1 M NaOH and 0.33 M CO(NH2)2 mixed electrolyte under AM1.5G illumination, which is 1.75 and 1.93 times those of TiO2/Ni(OH)2 deposited using a normal potentiostatic method with nickel salt solution and pristine TiO2, respectively. Ni0 doping can significantly decrease the charge transfer resistance and provide a more favorable distribution of density of states of Ni(OH)2 for the UOR. Furthermore, Ni0:Ni(OH)2 decorated TiO2 photoanodes exhibit good photocurrent retention during 12 h continuous testing. This work expands the preparation technique of urea catalysts and the strategy for developing highly efficient nickel-based catalysts.

Gleason score, surgical and distant metastasis are associated with cancer-specific survival and overall survival in middle aged high-risk prostate cancer: A population-based study.

Objective: According to statistics, patients with high-risk prostate cancer (PC) account for about 15% of prostate cancer diagnoses, and high-risk patients usually have a poor prognosis due to metastasis and recurrence and have a high mortality rate. Therefore, the accurate prediction of prognostic-related risk factors in middle-aged high-risk PC patients between 50 and 65 can help reduce patient mortality. We aimed to construct new nomograms for predicting cancer-specific survival (CSS) and Overall survival (OS) in middle-aged high-risk PC patients. Methods: Data for patients aged between 50 and 65 years old and diagnosed with high-risk PC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression models were used to identify independent risk factors for CSS and OS in patients. Nomograms predicting CSS and OS were developed based on multivariate Cox regression models. The concordance index (C-index), the area under the receiver operating characteristic curve (AUC), and the calibration curve are used to detect the accuracy and discrimination of the model. Decision curve analysis (DCA) is used to detect the potential clinical value of this model. Results: Between 2010 and 2018, 1,651 patients diagnosed with high-risk PC and aged 50-65 years were included. In this study, the training group (n = 1,146) and the validation group (n = 505) were randomly assigned in a ratio of 7:3. The results showed that M stage, Gleason (GS) and surgical mode were independent risk factors for CSS; marital status, T stage, M stage, surgical mode, and GS were independent risk factors for OS. The C-index for predicting CSS in the training and validation groups are 0.84 and 0.811, respectively; the C-index for predicting OS in the training and validation groups are 0.824 and 0.784, respectively. The AUC and the calibration curves also showed good accuracy and discrimination. Conclusions: We constructed new nomograms to predict CSS and OS in middle-aged high-risk PC patients. The prediction tools showed good accuracy and reliability, which can help clinicians and patients to make better clinical decisions.

A novel risk score model based on four angiogenesis long non-coding RNAs for prognosis evaluation of pancreatic adenocarcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to play significant roles in tumour angiogenesis which prominently facilitates pancreatic adenocarcinoma (PAAD) progression. METHODS: The clinical PAAD data were obtained from TCGA database and clinical specimens of 122 PAAD patients. The Molecular Signatures Database v4.0 was used to identify angiogenesis-related long non-coding RNAs (ARLNRs). Survival-related ARLNRs (sARLNRs) were further validated by univariate and multivariate COX regression analyses. The expressions of CASC8, AC015660.1, Z97832.2 and PAN3-AS1 in PAAD cell lines and tissues were examined by qPCR. The correlations between sARLNRs (CASC8 and AC015660.1) and clinicopathological characteristics of the 122 PAAD patients were analyzed by the chi-square test and Fisher's exact probability method. RESULTS: 590 lncRNAs were identified as ARLNRs, of which four sARLNRs were further used to establish an angiogenesis-related risk score model (ARRS), by which patients in the low-risk group have better survival probabilities than those in the high-risk group. The expression levels of CASC8 and AC015660.1 were significantly higher in PAAD cell lines and tumor tissues especially in patients with advanced grades and T-stages, while Z97832.2 and PAN3-AS1 were inverse. In addition, the higher expression of CASC8 and AC015660.1 prominently associated with the larger tumour size, and the more advanced grade and T-stage. However, the relevance between the sARLNRs (CASC8 and AC015660.1) expression and lymph node metastasis status was not significant. CONCLUSIONS: In the study, we illuminate the clinical significance, angiogenesis relevance and prognosis-predictive value of four sARLNRs for PAAD. The results build a bridge between sARLNRs and tumour vascularization, and also establish a reliable and accurate risk scoring model for PAAD antiangiogenic strategy.

Correction: ShRNA-Targeted COMMD7 Suppresses Hepatocellular Carcinoma Growth.

[This corrects the article DOI: 10.1371/journal.pone.0045412.].

Urinary proteome analysis of acute hypercoagulable state in rat model induced by ε-aminocaproic acid.

The hypercoagulable state occurs in a group of prothrombotic disorders associated with an increased risk for thromboembolic events, but it is difficult to diagnose due to the lack of available biomarkers. This study aimed to investigate systematic changes of urinary proteome in acute hypercoagulable state induced by certain antifibrinolytics. To reduce the effects of both genetic and environmental factors on the urinary proteome, we used a rat model of acute hypercoagulable state induced by an antifibrinolytic agent ε-aminocaproic acid, resembling human hypercoagulable state. Urine samples were collected during acute hypercoagulable state for analysis by liquid chromatography-tandem mass spectrometry (LCMS/MS). Of 65 significantly changed proteins in acute hypercoagulable state, 38 proteins had human orthologs, and 18 proteins were identified as stable in normal human urine. None of the identified proteins have been found to be clotting factors, but 4 proteins are known to be involved in the regulation of blood coagulation factors. Two proteins were verified as the markers associated with acute hypercoagulable state by Western blot analysis. In addition, four common differential urinary proteins have been found in acute hypercoagulable state induced by another antifibrinolytics tranexamic acid. These four proteins are potential biomarkers for early diagnosis of hypercoagulable state to prevent the development of thrombotic diseases.

SIRT1 facilitates hepatocellular carcinoma metastasis by promoting PGC-1α-mediated mitochondrial biogenesis.

SIRT1 is a multifaceted NAD+-dependent protein deacetylase known to act as a tumor promoter or suppressor in different cancers. Here, we describe a novel mechanism of SIRT1-induced hepatocellular carcinoma (HCC) metastasis. SIRT1 overexpression was frequently detected in human HCC specimens and was associated with microvascular invasion (P = 0.0039), advanced tumor node metastasis (TNM) stages (P = 0.0016), HCC recurrence (P = 0.021) and poor outcomes (P = 0.039). Lentivirus-mediated knockdown of SIRT1 in MHCC97H cells reduced invasion and metastasis in vitro and in vivo. SIRT1 depletion attenuated mitochondrial biogenesis and adenosine triphosphate (ATP) production but did not affect epithelial-mesenchymal transition. Elevated SIRT1 expression strongly correlated with the upregulation of PGC-1α in HCC specimens, and ectopic expression of SIRT1 increased PGC-1α levels. In cell assays and an orthotopic transplantation model, PGC-1α overexpression reversed the inhibitory effects of SIRT1 depletion on invasion and metastasis by enhancing mitochondrial biogenesis. These findings reveal the involvement of SIRT1 in HCC metastasis and provide a rationale for exploring therapeutic targets against the SIRT1/PGC-1α axis.

Identification of the typical miRNAs and target genes in hepatocellular carcinoma.

The aim of the present study was to identify miRNAs that were differentially expressed in hepatocellular carcinoma (HCC) by comparing normal and cancer tissue samples and to analyze the correlation of the target genes and HCC. The gene expression profile of GSE31383 was downloaded from the Gene Expression Omnibus database, including 19 samples, 9 normal and 10 from HCC tissue samples. The differentially­expressed miRNAs were identified with packages in R language and further analyzed using bioinformatics methods. Firstly, the verified targets of miRNAs were integrated in two miRNA databases: miRecords and miRTarBase, and the targets of the differentially­expressed miRNAs were obtained. The software STRING was then used to construct the interaction network of target genes. Finally, a functional enrichment analysis of the genes in the interaction network was conducted using the software Gestalt. Typical miR­224 and miR­214 were identified by comparing normal and cancer samples, each of which obtained 14 and 8 target genes, respectively. The functional enrichment analysis of the targets in the two groups highlighted the intracellular signaling cascade. In conclusion, the featured miRNAs (the upregulated miRNA­224 and downregulated miRNA­214) and their target genes are significant in the occurrence and development of HCC, which is likely to be significant for the identification of therapeutic targets and biomarkers to aid in the treatment of HCC.

[Expression and roles of the epithelial mesenchymal transition markers E-cadherin and vimentin in hepatocellular carcinoma].

OBJECTIVE: To determine the differential protein expressions of epithelial mesenchymal transition (EMT) markers E-cadherin and vimentin in hepatocellular carcinorma (HCC) and to investigate their correlation to the molecular mechanisms of metastasis to explore their potential utility as prognostic indicators of HCC. METHODS: Tumor tissues and patient-matched adjacent non-tumor tissues were collected from individuals diagnosed with HCC. E-cadherin and vimentin protein expressions in the tissue specimens were quantified by western blot with densitometry of fluorescence emission and comparatively analyzed to determine the associations with molecular and clinical features. The expressions of E-cadherin and vimentin, as well as the other EMT-related protein Twist, were also detected in the tissue specimens by immunohistochemistry. Statistical analyses were carried out by paired-samples t-test, Mann-Whitney test, and Spearman rank correlation analysis. RESULTS: E-cadherin expression was significantly lower in tumor tissues (0.082 +/- 0.063 vs. adjacent non-tumor tissues: 0.226 +/- 0.215, t = -4.050, P less than 0.01), lower in patients with portal vein tumor thrombus (vs. non-thrombic HCC patients, P = 0.001), and correlated with TNM stage (III/IV > I/II, P = 0.003). Vimentin expression was significantly higher in tumor tissues (vs. adjacent non-tumor tissues, P = 0.002), negatively correlated with E-cadherin expression (t = -0.509, P = 0.004), and closely associated with some clinical parameters, such as portal vein tumor thrombus (P less than 0.01), TNM stage (P less than 0.01), and Milan criteria (P = 0.005). Immunohistochemistry showed that E-cadherin expression was very weak in tumors but very strong in the cell membranes of non-tumor tissues, and that vimentin and Twist expressions were strong in tumors but undetectable in non-tumor tissue. CONCLUSION: Expression levels of the EMT markers E-cadherin and vimentin in HCC are related to clinical parameters, including portal vein tumor thrombus and TNM stage, and may represent useful prognostic markers of metastasis.

Bioinformatics analysis reveals potential candidate drugs for HCC.

In our study, we used the GSE17967 series to identify differentially expressed genes between cirrhosis and hepatocellular carcinoma, aiming to analyse the mechanism of the progression of cirrhosis to hepatocellular carcinoma and identify the sub-pathways closely related to this progression, and find the small molecule drugs to interfere this progression. From the result of our study, we find that many small molecule drugs closely related with carcinoma have been linked by our method. We also find some new small molecule drugs related to this progression. It is demonstrated that bioinformatics analysis is useful in identification of the candidate drugs in hepatocellular carcinoma.

Development of QSAR-Improved Statistical Potential for the Structure-Based Analysis of ProteinPeptide Binding Affinities.

Proteinpeptide interactions have recently been found to play an essential role in constructing intracellular signaling networks. Understanding the molecular mechanism of such interactions and identification of the interacting partners would be of great value for developing peptide therapeutics against many severe diseases such as cancer. In this study, we describe a structure-based, general-purpose strategy for fast and reliably predicting proteinpeptide binding affinities. This strategy combines unsupervised knowledge-based statistical potential derived from 505 interfacially diverse, non-redundant proteinpeptide complex structures and supervised quantitative structure-activity relationship (QSAR) modeling trained by 250 proteinpeptide interactions with known structure and affinity data. The built partial least squares (PLS) model is confirmed to have high stability and predictive power by using internal 5-fold cross-validation and rigorous Monte Carlo cross-validation (MCCV). The model is further employed to analyze two large groups of HLA- and SH3-binding peptides based upon computationally modeled structures. Satisfactorily, although the PLS model is originally trained with dissociation constants (Kd ) of proteinpeptide binding, it shows a good correlation with other two affinity qualities, i.e. SPOT signal intensities (BLU) and half maximal competitive concentrations (IC50 ). Furthermore, we perform systematic comparisons of our method with several widely used, representative affinity predictors, including molecular mechanics-based MM-PB/SA, knowledge-based DFIRE and docking score HADDOCK, on a small panel of elaborately selected proteinpeptide systems. It is demonstrated that (i) the QSAR-improved statistical potential exhibits a comparable predictive performance with but can work faster than these traditional methods, and (ii) the crystal structure-derived statistical potential also supports the modeled and solution structures of proteinpeptide complexes. We expect that this hybrid method can be exploited as a new scoring tool to facilitate, for example, peptide docking and virtual screening.

Use of fast conformational sampling to improve the characterization of VEGF A-peptide interactions.

Protein-peptide interaction is fundamentally important for signal transduction, transcription regulation, protein degradation, cell regeneration, and immune response. Here, we report the use of a fast conformational sampling strategy to improve the prediction of protein-peptide binding affinity. This method generates hundreds of alternative conformers for a protein-peptide complex and then performs classical MM-PB/SA analysis over these conformers to derive a consistent binding energy expression for the complex. We show a proof-of-concept study on vascular endothelial growth factor A (VEGF A) interaction with its peptide ligands. The structures of VEGF A complexed with 13 peptides are modeled with a virtual mutagenesis protocol and their binding energies are subsequently calculated by using the conformational sampling-based method. A good linear correlation between the calculated and experimental values is observed, and we demonstrate that the correlation could be further improved by fitting the decomposed energy terms to experimentally measured affinity. Furthermore, the obtained results are discussed in detail in order to elucidate the structural basis and energetic implication underlying VEGF A-peptide recognition and association. We also give a detailed comparison between the proposed method and other widely used approaches, from which it is suggested that our method exhibits a good compromise between the effectiveness and efficiency in evaluating protein-peptide affinity.

ShRNA-targeted COMMD7 suppresses hepatocellular carcinoma growth.

BACKGROUND: COMMD7 is a newly identified gene overexpressed in hepatocellular carcinoma (HCC) and associated with tumor invasion and poor prognosis. We aim to examine the biological function of COMMD7 in HCC by shRNA silencing. METHODS: COMMD7 expressions were examined in human HCC cell lines HepG2, Huh7, Hep3B, HLE, HLF, SK-Hep-1 and PLC/PRF/5 cells. Recombinant pGenesil-COMMD7-shRNA was transfected into COMMD7-abundant HepG2 cells to silence COMMD7 expression. The effects of COMMD7 silencing on HepG2 cell proliferation in vitro and xenograft tumor growth in vivo were evaluated. Flow cytometry profiling was used to detect the presence of apoptosis in COMMD7-silenced HepG2 cells and to differentiate cell cycle distribution. Electrophoretic mobility shift assay and luciferase reporter assays to examine the activities of nuclear factor-kappaB (NF-κB) signaling pathways in response to tumor necrosis factor (TNF)-α in COMMD7-silenced HepG2 cells. RESULTS: COMMD7 expression level was abundance in HepG2 and SK-Hep-1 cells. COMMD7 was aberrantly overexpressed in HepG2 cells, whilst pGenesil-COMMD7-shRNA exhibited a maximal inhibition rate of 75%. COMMD7 silencing significantly reduced HepG2 cell proliferation and colony formation. The knockdown of COMMD7 resulted in an increased apoptosis and cell cycle arrest at S-phase. COMMD7 knockdown also exhibited an antineoplastic effect in vivo, which manifested as tumor xenograft growth retardation. COMMD7 silencing also suppressed the responsiveness of NF-κB signaling pathway to the stimulation with TNF-α in vitro. Moreover, the similar suppressive effects of COMMD7 silence on SK-Hep-1 cells were also observed. CONCLUSIONS: COMMD7 contributes to HCC progression by reducing cell apoptosis and overcoming cell cycle arrest. The proliferative and antiapoptotic effects of COMMD7 may be mediated by NF-κB signaling pathway.

A case of wedge resection of duodenum for massive gastrointestinal bleeding due to duodenal metastasis by renal cell carcinoma.

BACKGROUND: Gastrointestinal bleeding due to duodenal metastasis from renal cell carcinoma is extremely rare. Several previous reports have shown that embolic therapy or pancreatoduodenectomy (radical surgical resection) could be effective in controlling this type of clinical complication. Management is entirely dependent on the general condition and concurrent metastases at other sites. Optimizing the therapeutic strategies thus deserves further discussion and exploration. METHODS: In this report, we describe a patient with severe co-morbidities who underwent successful palliative wedge resection of duodenum and direct duodenal wall defect repair without reconstruction of duodeno-jejunostomy for acute upper digestive tract hemorrhage caused by duodenal metastasis from renal clear cell carcinoma. RESULTS: The patient recovered uneventfully and did not experience rebleeding and frequent vomiting after surgery. Since then (1.5 years) he has had no evidence of rebleeding. CONCLUSIONS: Gastrointestinal bleeding due to duodenal metastasis of RCC may benefit from emergent resection even in the presence of severe co-morbidities, and for palliative treatment.

BC047440 overexpression is a risk factor for tumor invasion and poor prognosis in hepatocellular carcinoma.

BACKGROUND/AIMS: The aim of this study was to investigate the relationship between a new tumor-relative protein (BC047440) expression and clinic pathological parameters of hepatocellular carcinoma (HCC), and to evaluate the prognostic value of BC047440 for HCC patients. METHODS: Following the prokaryotic expression and polyclonal antibodies generation of BC047440, two methods, including western blot and immunohistochemical staining were employed to detect BC047440 expression in 68 HCC specimens. The correlation between BC047440 expression and clinicopathologic outcome, and prognostic value of BC047440 for HCC patients were analyzed. RESULTS: The polyclonal antibodies could effectively recognize endogenous BC047440 in HCC tissues. Western blot and immunohistochemical staining revealed that the expression of BC047440 protein was higher in HCCs than that in adjacent tissues and normal liver tissues. Statistical analysis showed that there was a good correlation between BC047440 expression and tumor size and invasion of HCC. HCC patients with BC047440-positive expression showed a significantly poor prognosis than those with BC047440-negative expression. CONCLUSIONS: BC047440 has a regulatory function in progress of HCC and it may become a helpful indicator in handling HCC treatment and judging invasion.

Surgical separation of shared liver with cotton tourniquets in conjoined twins: simple and effective hemostasis.

OBJECTIVE: Surgical separation of the fused liver is extremely risky and sometimes life-threatening in conjoined twins because of the potential risks of hypovolemia and hemorrhagic shock. METHODS: Three pairs of symmetrical conjoined twins sharing fused livers were successfully separated by using a simple but effective local blockade measure without disturbing the portal circulation. RESULTS: The volume of intraoperative blood loss was minimal, and no major complications occurred. All the separated babies survived the procedure and remained healthy, both physically and mentally, after discharge. Two babies died of pneumonia associated with their preexisting cardiac defects. CONCLUSIONS: Cotton tourniquets temporally and securely blocked the local blood supply to the narrow gap dissecting interface with minimal interference with the remaining segments, in addition to orienting the transection of the fused liver and minimizing blood loss from the liver dissection.