Transformation of metoprolol in UV/PDS process: Role and mechanisms of degradation and polymerization.

Advanced oxidation processes for the treatment of organic pollutants in wastewater suffer from difficulties in mineralization, potential risks of dissolved residues, and high oxidant consumption. In this study, radical-initiated polymerization is dominated in an UV/peroxydisulfate (PDS) process to eliminate organic pollutant of pharmaceutical metoprolol (MTP). Compared with an ideal degradation-based UV/PDS process, the present process can save four fifths of PDS consumption at the same dissolved organic carbon removal of 47.3%. Simultaneously, organic carbon can be recovered from aqueous solution by separating solid polymers at a ratio of 50% of the initial chemical oxygen demand. The chemical structure of products was analyzed to infer the transformation pathways of MTP. Unlike previous studies on simple organic pollutants that the polymerization can occur independently, the polymerization of MTP is dependent on the partial degradation of MTP, and the main monomer in polymerization is a dominant degradation product (4-(2-methoxyethyl)-phenol, denoted as DP151). The separated solid polymers are formed by repeated oxidation and coupling of DP151 or its derivatives through a series of intermediate oligomers. This proof-of-concept study demonstrates the advantage of polymerization-dominated mechanism on dealing with large organic molecules with complex structures, as well as the potential of UV/PDS process for simultaneous organic pollution reduction and organic carbon recovery from aqueous solution.

Catalytic ozonation of reverse osmosis concentrate from coking wastewater reuse by surface oxidation over Mn-Ce/γ-Al2O3: Effluent organic matter transformation and its catalytic mechanism.

Degradation of organics in high-salinity wastewater is beneficial to meeting the requirement of zero liquid discharge for coking wastewater treatment. Creating efficient and stable performance catalysts for high-salinity wastewater treatment is vital in catalytic ozonation process. Compared with ozonation alone, Mn and Ce co-doped γ-Al2O3 could remarkably enhance activities of catalytic ozonation for chemical oxygen demand (COD) removal (38.9%) of brine derived from a two-stage reverse osmosis treatment. Experimental and theoretical calculation results indicate that introducing Mn could increase the active points of catalyst surface, and introducing Ce could optimize d-band electronic structures and promote the electron transport capacity, enhancing HO• bound to the catalyst surface ([HO•]ads) generation. [HO•]ads plays key roles for degrading the intermediates and transfer them into low molecular weight organics, and further decrease COD, molecular weights and number of organics in reverse osmosis concentrate. Under the same reaction conditions, the presence of Mn/γ-Al2O3 catalyst can reduce ΔO3/ΔCOD by at least 37.6% compared to ozonation alone. Furthermore, Mn-Ce/γ-Al2O3 catalytic ozonation can reduce the ΔO3/ΔCOD from 2.6 of Mn/γ-Al2O3 catalytic ozonation to 0.9 in the case of achieving similar COD removal. Catalytic ozonation has the potential to treat reverse osmosis concentrate derived from bio-treated coking wastewater reclamation.

Spatial-temporally and industrially heterogeneous effects of new infrastructure construction on fostering emerging industries in Chinese cities.

New infrastructure construction stemming from the new waves of technological revolution worldwide is exemplified by 5G base stations, big data centers, and ultra-high voltage. It has aroused extensive academic and policy interests in recent years, especially due to its beneficial role in empowering regional novel economic dynamics. However, this argument is still too general to capture the nuanced effects of new infrastructure construction on fostering emerging industries in specific spatial-temporal and industrial contexts, which is left for geographers to take up. This paper focuses on the spatial-temporally and industrially heterogeneous effects of new infrastructure construction on fostering four distinctive emerging industries in major Chinese cities over the last decade. It reveals that new infrastructure construction and emerging industries have experienced rapid development in major Chinese cities, with geographical agglomeration in national central cities with advanced economic development level. It is empirically demonstrated that new infrastructure construction can facilitate the development of emerging industries in major Chinese cities, while significant spatial-temporal heterogeneity characterizes the contributory forces. Furthermore, artificial intelligence as a Key Enabling Technology, robotics as a kind of hardware-featured industry, software-as-a-service as a software-centered industry, and blockchain as a networking-oriented industry vary markedly in the extent and the ways in which they benefit from new infrastructure construction, and they consequently exhibit industrial sensitivity to spatial-temporal heterogeneity in the fostering effects.

Insight into micropollutant abatement during ultraviolet light-emitting diode combined electrochemical process: Reaction mechanism, contributions of reactive species and degradation routes.

Electrochemical process coupling with ultraviolet light-emitting diode for micropollutant abatement was evaluated in the treatment of wastewater containing Cl-. Four representative micropollutants, atrazine, primidone, ibuprofen and carbamazepine, were selected as target compounds. The impacts of operating conditions and water matrix on micropollutant degradation were investigated. Fluorescence excitation-emission matrix spectroscopy spectra and high performance size exclusion chromatography were employed to characterize the transformation of effluent organic matter in treatment. The degradation efficiencies of atrazine, primidone, ibuprofen and carbamazepine are 83.6 %, 80.6 %, 68.7 % and 99.8 % after 15 min treatment, respectively. The increment of current, Cl- concentration and ultraviolet irradiance promote the micropollutant degradation. However, the presence of bicarbonate and humic acid inhibit micropollutant degradation. The mechanism of micropollutant abatement was elaborated based on reactive species contributions, density functional theory calculation and degradation routes. Free radicals (HO•, Cl•, ClO• and Cl2•-) could be generated by chlorine photolysis and subsequent propagation reactions. The concentrations of HO• and Cl• are 1.14 × 10-13 M and 2.0 × 10-14 M in optimal condition, respectively, and the total contributions of HO• and Cl• for the degradation of atrazine, primidone, ibuprofen and carbamazepine are 24 %, 48 %, 70 % and 43 %, respectively. The degradation routes of four micropollutants are elucidated based on intermediate identification, Fukui function and frontier orbital theory. Micropollutants can be effectively degraded in actual wastewater effluent, and the small molecule compound proportion increases during effluent organic matter evolution. Compared with photolysis and electrolysis, the coupling of the two processes has potential for energy saving in micropollutant degradation, which shed light on the prospects of ultraviolet light-emitting diode coupling with electrochemical process for effluent treatment.

Abatement of Aromatic Contaminants from Wastewater by a Heat/Persulfate Process Based on a Polymerization Mechanism.

A novel approach to the abatement of pollutants consisting of their conversion to separable solid polymers is explored by a heat/persulfate (PDS) process for the treatment of high-temperature wastewaters. During this process, a simultaneous decontamination and carbon recovery can be achieved with minimal use of PDS, which is significantly different from conventional degradation processes. The feasibility of this process is demonstrated by eight kinds of typical organic pollutants and by a real coking wastewater. For the treatment of the selected pollutants, 30.2-91.9% DOC abatement was achieved with 24.8-91.2% carbon recovery; meanwhile, only 5.2-47.0% of PDS was consumed compared to a conventional degradation process. For the treatment of a real coking wastewater, 71.0% DOC abatement was achieved with 66.0% carbon recovery. With phenol as a representative compound, our polymerization-based heat/PDS process is applicable in a wide pH range (3.5-9.0) with a carbon recovery of >87%. Both SO4•- and HO• can be initiators for polymerization, with different contribution ratios under various conditions. Phenol monomers are semioxidized to form phenolic radicals, which are polymerized via chain transfer or chain growth processes to form separable solid phenol polymers, benzenediol polymers, and cross-linked polymers.

Organics abatement and recovery from wastewater by a polymerization-based electrochemically assisted persulfate process: Promotion effect of chloride ion and its mechanism.

Ubiquitous chloride ion (Cl-) in wastewaters usually inhibits the degradation of organic contaminants and generates numerous toxic chlorinated products in conventional degradation-based advanced oxidation processes (AOPs). Herein, a more Cl- tolerant polymerization-based electrochemical AOP for organic contaminants abatement and simultaneous organic resource recovery was demonstrated with eight typical organic contaminants and two real industrial wastewaters for the first time. This process can significantly promote dissolved organic carbon (DOC) abatement in the presence of Cl-, differing greatly from conventional degradation-based processes. Compared to sulfate radical (SO4•-) (or hydroxyl radical (HO•)), dichloride radical (Cl2•-) derived from Cl- has moderate reactivity towards most contaminants, which facilitates the organics polymerization as it ensures the formation of polymerizable organic radicals while inhibiting their excessive degradation. Thus, high DOC abatement (over 75 %) and high organic resource recovery ratio (48-79 % separable organic-polymer yield) can be achieved for most contaminants. Both soluble chlorinated compounds and solid chlorinated polymers are formed in the presence of Cl-. The chlorinated products (e.g. chlorophenols) can be polymerized as new monomers, thus the concentration of dissolved organic chlorinated products is much lower than that in conventional degradation-based process. The tolerance of the present process to Cl- is tested in real coking wastewaters, and exceeding 60 % of the abated chemical oxygen demand (COD) is obtained in the form of recoverable organic-polymers.

Treatment of contaminants by a cathode/FeIII/peroxydisulfate process: Formation of suspended solid organic-polymers.

Treatment of highly contaminated wastewaters containing refractory or toxic organic contaminants (e.g. industrial wastewaters) is becoming a global challenge. Most technologies focus on efficient degradation of organic contaminants. Here we improve the cathode/FeIII/peroxydisulfate (PDS) technology by turning down the current density and develop an innovative mechanism for organic contaminants abatement, namely polymerization rather than degradation, which allows simultaneous contaminants removal and resource recovery from wastewater. This polymerization leads to organic-particles (suspended solid organic-polymers) formation in bulk solution, which is demonstrated by eight kinds of representative organic contaminants. Taking phenol as a representative, 83% of PDS is saved compared to degradation process, with 87.2% of DOC removal. The formed suspended solid organic-polymers occupy 59.2% of COD of the original organics in solution, and can be easily separated from aqueous solution by sedimentation or filtration. The separated organic-polymers are a series of polymers coupled by phenolic monomers, as confirmed by FTIR and ESI-MS analyzes. The energy contained in the recovered organic polymers (4.76 × 10-5 kWh for 100 mL of 1 mM phenol solution in this study) can fully compensate the consumed electrical energy (2.8 × 10-5 kWh) in the treatment process. A representative polymerization model for this process is established, in which the SO4•- and HO• generated from PDS activation initiate the polymerization and improve the polymerization degree by the production of oligomer intermediates. A practical coking wastewater treatment is carried out to verify the research results and get positive feedback, with 56.0% of DOC abatement and the suspended solid organic-polymers accounts for 42.5% of the total COD in the raw wastewater. The energy consumption (47 kWh/kg COD, including electricity and PDS cost) is lower than the values in previous reports. This study provides a novel method for industrial wastewater treatment based on polymerization mechanism, which is expected to recover resources while removing pollutants with low consumption.

Clinical significance of mitogen-activated protein kinase kinase kinases in hepatitis B virus -related hepatocellular carcinoma and underlying mechanism exploration.

The purpose of this research was to explore the diagnostic/prognostic significance and prospective molecular mechanisms of mitogen-activated protein kinase kinase kinases (MAP3Ks) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Diagnostic/prognostic significance of MAP3Ks was screened in the GSE1450 data set and validated in the Guangxi cohort. Various bioinformatics tools were used to explore the biological functions of prognosis-related genes. Subsequently, molecular biology assays were used to verify the biological functions and molecular mechanisms of specific gene. MAP3K9 was observed to be differentially expressed in HCC and adjacent tissues with satisfactory diagnostic value. It was discovered in survival analysis that MAP3K13 and MAP3K15 were associated with overall survival (OS) of patients with HBV-related HCC in the GSE1450 data set and the Guangxi cohort. Nomograms were established based on prognosis-related genes and clinical factors for individualized risk assessment. The assays on HCC cells demonstrated that MAP3K13 regulated the death and proliferation of HCC cells by activating the JNK pathway and inducing the expression of apoptosis-related factors. In conclusion, our results suggested that MAP3K9 might serve as a diagnostic biomarker in HBV-related HCC and MAP3K13 and MAP3K15 might serve as useful prognostic biomarkers. Besides, cytological assays prompted that MAP3K13 might impact the prognosis of HCC by regulating the JNK pathway and inducing apoptosis.

Applying fulvic acid for sediment metals remediation: Mechanism, factors, and prospect.

Fulvic acid (FA) has been shown to play a decisive role in controlling the environmental geochemical behavior of metals. As a green and natural microbial metabolite, FA is widely used in environmental remediation because of its good adsorption complexation and redox ability. This paper introduces the reaction mechanism and properties of FA with metals, and reviews the progress of research on the remediation of metal pollutant by FA through physicochemical remediation and bioremediation. FA can control the biotoxicity and migration ability of some metals, such as Pb, Cr, Hg, Cd, and As, through adsorption complexation and redox reactions. The concentration, molecular weight, and source are the main factors that determine the remediation ability of FA. In addition, the ambient pH, temperature, metal ion concentrations, and competing components in sediment environments have significant effects on the extent and rate of a reaction between metals and FA during the remediation process. Finally, we summarize the challenges that this promising environmental remediation tool may face. The research directions of FA in the field of metals ecological remediation are also prospected. This review can provide new ideas and directions for the research of remediation of metals contaminants in sediments.

SOX4 as biomarker in hepatitis B virus-associated hepatocellular carcinoma.

Background: Hepatitis B virus infection is associated with liver disease, including cancers. In this study, we assessed the power of sex-determining region Y (SRY)-related high-mobility group (HMG)-box 4(SOX4) gene to predict the clinical course of hepatocellular carcinoma (HCC). Methods: To evaluate the differential expression of SOX4 and its diagnostic and prognostic potential in HCC, we analyzed the GSE14520 dataset. Stratified analysis and joint-effect analysis were done using SOX4 and clinical factor. We then designed a nomogram for predicting the clinical course of HCC. Differential SOX4 expression and its correlation with tumor stage as well as its diagnostic and prognostic value were analyzed on the oncomine and GEPIA websites. Gene set enrichment analysis was explored as well as candidate gene ontology and metabolic pathways modulated by in SOX4 HCC. Results: Our analysis revealed that the level of SOX4 was significantly upregulated in tumor issue (P <0.001). This observation was validated through oncomine dataset and MERAV analysis (all P <0.05). Diagnostic receiver operating characteristic (ROC) analysis of SOX4 suggested it has diagnostic potential in HCC (GSE14520 dataset: P <0.001, area under curve (AUC) = 0.782; Oncomine: (Wurmbach dataset) P = 0.002, AUC = 0.831 and (Mas dataset) P <0.001, AUC = 0.947). In addition, SOX4 exhibited high correlation with overall survival of HBV-associated HCC (adjusted P = 0.004, hazard ratio (HR) (95% confidence interval (CI)) = 2.055 (1.261-3.349) and recurrence-free survival (adjusted P = 0.008, HR (95% CI) = 1.721 (1.151-2.574). These observations which were verified by GEPIA analysis for overall survival (P = 0.007) and recurrence-free survival (P= 0.096). Gene enrichment analysis revealed that affected processes included lymphocyte differentiation, pancreatic endocrine pathways, and insulin signaling pathway. SOX4 prognostic value was evaluated using nomogram analysis for HCC 1, 3, and 5-year, survival. Conclusion: Differential SOX4 expression presents an avenue of diagnosing and predicting clinical course of HCC. In HCC, SOX4 may affect TP53 metabolic processes, lymphocyte differentiation and the insulin signaling pathway.

Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms.

BACKGROUND: This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). METHODS: A total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis. RESULTS: In TCGA database, high expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway. CONCLUSION: GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.

Determination methods for steady-state concentrations of HO• and SO4•- in electrochemical advanced oxidation processes.

Competitive kinetics and scavenging assay are commonly used for radical quantification. However, the accuracy of the two methods has been challenged in electrochemical advanced oxidation processes (EAOPs) since the strong reactivity of electrode against organic indicators may disrupt the quantitative relationship between indicator consumption and radical concentration. The present study focused on screening suitable indicators and developing suitable methods for determining the steady-state concentrations of SO4•- and HO• ([SO4•-]ss and [HO•]ss) in several EAOPs for water treatment based on competitive kinetics and scavenging assay. The applicability of the modified methods and available indicators were investigated through experimental and kinetic analysis. In anode alone process, the competitive kinetics was more appropriate than scavenging assay and benzoic acid (BA) met the basic requirement of being a competitor to determine the [HO•]ss. In cathode alone process, BA was more resistant to interfering factors than other competitors (ibuprofen, atrazine and nitrobenzene) and its reaction rate involved only the radical oxidation even when the reaction conditions varied over a wide range. Therefore, the [HO•]ss could be obtained by the competitive kinetic equation of BA when HO• existed alone. When HO• coexisted with SO4•-, a two-step method combining scavenging assay and competitive kinetics was proposed to measure [SO4•-]ss and [HO•]ss, in which tert-butyl alcohol and BA were added as scavenger and competitor, respectively. Furthermore, the reliability of each approach was verified by the experimental results and kinetic analysis.

Phosphate sequestration by magnetic La-impregnated bentonite granules: A combined experimental and DFT study.

To use the lanthanum hydroxide (La(OH)3) as a low-cost, highly-efficient, and recyclable adsorbent, it could be embedded on a magnetic substance to improve its physical features and lower the overall cost. Herein, novel millimetric-size magnetic lanthanum-modified bentonite (La-MB) granules were fabricated for P sequestration, and the adsorption performance and mechanisms were systematic studied. The maximum capacity of P uptake by La-MB was up to 48.4 mg/g, which was higher than many previous reported La-based adsorbents. Moreover, the enhanced uptake of P was achieved over a wide pH range (3-9) and in the coexistence of common anions (Cl-, NO3-, and SO42-). Besides, the exhausted La-MB can be effectively regenerated by 5 mol/L NaOH with about 94.5% desorption efficiency and 60.8% uptake capacity remained during 5 cycles. The La-MB also exhibited excellent performance of anti-interference in two kinds of real wastewaters. The postsorption characterization and DFT calculations revealed that the electrostatic interaction and chemical precipitation jointly facilitated phosphate sequestration by La-MB during the rapid sorption phase, while ligand exchange and complexation reaction played more important roles than others during the slow sorption step. The electrostatic interaction not only effectively promoted the ligand exchange, and also further accelerated chemical precipitation via the formation of LaPO4 during the whole process of phosphate uptake. Overall, millimetric La-MB is considered to have great potential for engineering application, and this work also provides new insights into the molecular-level mechanism of phosphate sequestration by La-MB.

Oncogene PLCE1 may be a diagnostic biomarker and prognostic biomarker by influencing cell cycle, proliferation, migration, and invasion ability in hepatocellular carcinoma cell lines.

Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide. HCC has traits of late diagnosis and high recurrence. This study explored potential diagnosis and prognosis significance of phospholipase C epsilon 1 (PLCE1) in HCC. The messenger RNA (mRNA) levels and diagnostic value of PLCE1 were determined by real-time polymerase chain reaction and online databases GEPIA, oncomine, and GSE14520 data set. Survival analysis used the Kaplan-Meier Plotter website. Cell cycle, proliferation, migration, and invasion assays were performed with downregulated PLCE1 expression in HCC-M and HepG2 cell lines. PLCE1 was differentially expressed and highly expressed in tumors and had low expression in nontumor tissues (all p < .05). The diagnostic value of PLCE1 was validated with the datasets (all p < .01, all areas under curves > 0.7). PLCE1 mRNA expression was associated with the overall and relapse-free survival (both p < .05). Functional experiments indicated that downregulation of PLCE1 expression led to increased G1 stage in cell cycle and decreased cell proliferation, migration, and invasion compared with a negative control group (all p ≤ .05). The oncogene PLCE1 was differentially expressed in HCC and non-HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.

Comprehensive investigation of p53, p21, nm23, and VEGF expression in hepatitis B virus-related hepatocellular carcinoma overall survival after hepatectomy.

Objective: The goal of our current study is to assess the immunohistochemical of p53, p21, nm23, and VEGF expression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) prognosis after hepatectomy, as well as the prospective molecular mechanisms of prognostic indicator. Methods: There were 419 HBV-related HCC patients who were from southern China of Guangxi province and were used to evaluate the immunohistochemical expression for these biomarkers in prognosis. A genome-wide expression microarray dataset of HBV-related HCC were obtained from GSE14520. Results: In our study, the expression of p53, p21, and nm23 in cancer tissues of patients with hepatitis B-related hepatocellular carcinoma did not affected the clinical outcome of 2 years, 5 years or overall. Patients with high expression of VEGF had a worse overall survival after 2 years of surgery than patients with low expression (adjusted P=0.040, adjusted HR = 1.652, 95% CI = 1.024-2.665). Survival analysis of VEGF in GSE14520 cohort also demonstrated that VEGF mRNA expression also significantly associated with HBV-related HCC OS (adjusted P=0.035, adjusted HR =1.651, 95% CI =1.035-2.634). The prospective molecular mechanisms by co-expression analysis suggested that VEGF might be correlated to regulation of cell proliferation, cell growth and apoptotic process, Rap1 signaling pathway, HIF-1 signaling pathway, PPAR signaling pathway, cell cycle. Whereas the GSEA suggested that VEGF might involve in the regulation of HIF and HIF1A pathway, and TP53 regulation pathway. Conclusion: Our findings suggested that VEGF might be a prognostic indicator of HBV-related HCC, and we also identified the VEGF prospective molecular mechanisms through the whole genome co-expression and GSEA approaches.

Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma.

Objective: Our study is aim to explore potential key biomarkers and pathways in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using genome-wide expression profile dataset and methods. Methods: Dataset from the GSE14520 is used as the training cohort and The Cancer Genome Atlas dataset as the validation cohort. Differentially expressed genes (DEGs) screening were performed by the limma package. Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), gene ontology, the Kyoto Encyclopedia of Genes and Genomes, and risk score model were used for pathway and genes identification. Results: GSEA revealed that several pathways and biological processes are associated with hepatocarcinogenesis, such as the cell cycle, DNA repair, and p53 pathway. A total of 160 DEGs were identified. The enriched functions and pathways of the DEGs included toxic substance decomposition and metabolism processes, and the P450 and p53 pathways. Eleven of the DEGs were identified as hub DEGs in the WGCNA. In survival analysis of hub DEGs, high expression of PRC1 and TOP2A were significantly associated with poor clinical outcome of HBV-related HCC, and shown a good performance in HBV-related HCC diagnosis. The prognostic signature consisting of PRC1 and TOP2A also doing well in the prediction of HBV-related HCC prognosis. The diagnostic and prognostic values of PRC1 and TOP2A was confirmed in TCGA HCC patients. Conclusions: Key biomarkers and pathways identified in the present study may enhance the comprehend of the molecular mechanisms underlying hepatocarcinogenesis. Additionally, mRNA expression of PRC1 and TOP2A may serve as potential diagnostic and prognostic biomarkers for HBV-related HCC.

Diagnostic and prognostic biomarkers of Human Leukocyte Antigen complex for hepatitis B virus-related hepatocellular carcinoma.

Background: Hepatitis B virus infection had been identified its relationship with liver diseases, including liver tumors. We aimed to explore diagnostic and prognostic values between the Human Leukocyte Antigen (HLA) complex and hepatocellular carcinoma (HCC). Methods: We used the GSE14520 dataset to explore diagnostic and prognostic significance between HLA complex and HCC. A nomogram was constructed to predict survival probability of HCC prognosis. Gene set enrichment analysis was explored using gene ontologies and metabolic pathways. Validation of prognostic values of the HLA complex was performed in the Kaplan-Meier Plotter website. Results: We found that HLA-C showed the diagnostic value (P <0.0001, area under curve: 0.784, sensitivity: 93.14%, specificity: 62.26%). In addition, HLA-DQA1 and HLA-F showed prognostic values for overall survival, and HLA-A, HLA-C, HLA-DPA1 and HLA-DQA1 showed prognostic values for recurrence-free survival (all P ≤ 0.05, elevated 0.927, 0.992, 1.023, 0.918, 0.937 multiples compared to non-tumor tissues, respectively). Gene set enrichment analysis found that they were involved in antigen processing and toll like receptor signalling pathway, etc. The nomogram was evaluated for survival probability of HCC prognosis. Validation analysis indicated that HLA-C, HLA-DPA1, HLA-E, HLA-F and HLA-G were associated with HCC prognosis of overall survival (all P ≤ 0.05, elevated 0.988 and 0.997 multiples compared to non-tumor tissues, respectively). Conclusion: HLA-C might be a diagnostic and prognostic biomarker for HCC. HLA-DPA1 and HLA-F might be prognostic biomarkers for HCC.

Analysis of clinical significance and prospective molecular mechanism of main elements of the JAK/STAT pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one the most common malignancies and has poor prognosis in patients. The aim of the present study is to explore the clinical significance of the main genes involved in the Janus kinase (JAK)­signal transducer and activator of transcription (STAT) pathway in HCC. GSE14520, a training cohort containing 212 hepatitis B virus­infected HCC patients from the Gene Expression Omnibus database, and data from The Cancer Genome Atlas as a validation cohort containing 370 HCC patients, were used to analyze the diagnostic and prognostic significance for HCC. Joint­effect analyses were performed to determine diagnostic and prognostic significance. Nomograms and risk score models were constructed to predict HCC prognosis using the two cohorts. Additionally, molecular mechanism analysis was performed for the two cohorts. Prognosis­associated genes in the two cohorts were further validated for differential expression using reverse transcription­quantitative polymerase chain reaction of 21 pairs of hepatitis B virus­infected HCC samples. JAK2, TYK2, STAT3, STAT4 and STAT5B had diagnostic significance in the two cohorts (all area under curves >0.5; P≤0.05). In addition, JAK2, STAT5A, STAT6 exhibited prognostic significance in both cohorts (all adjusted P≤0.05). Furthermore, joint­effect analysis had advantages over using one gene alone. Molecular mechanism analyses confirmed that STAT6 was enriched in pathways and terms associated with the cell cycle, cell division and lipid metabolism. Nomograms and risk score models had advantages for HCC prognosis prediction. When validated in 21 pairs of HCC and non­tumor tissue, STAT6 was differentially expressed, whereas JAK2 was not differentially expressed. In conclusion, JAK2, STAT5A and STAT6 may be potential prognostic biomarkers for HCC. JAK2, TYK2, STAT3, STAT4 and STAT5B may be potential diagnostic biomarkers for HCC. STAT6 has a role in HCC that may be mediated via effects on the cell cycle, cell division and lipid metabolism.

Prognostic value of Kinesin-4 family genes mRNA expression in early-stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy.

BACKGROUND: The aim of this study was to investigate the potential prognostic value of Kinesin-4 family genes mRNA expression in early-stage pancreatic ductal adenocarcinoma (PDAC) patients after pancreaticoduodenectomy. METHODS: Kaplan-Meier survival analysis method with log-rank test and Cox proportional hazards regression analysis were performed to figure out the association between Kinesin-4 family genes expression and PDAC patients overall survival time. Joint-effect survival analysis and stratified survival analysis were carried out to assess the prognosis prediction value of prognosis-related gene. Nomogram was constructed for the individualized prognosis prediction. In addition, we had used the gene set enrichment analysis and genome-wide co-expression analysis to further explore the potential mechanism. RESULTS: KIF21A expression level was significantly associated with PDAC patient clinical prognosis outcome and patient with a high expression of KIF21A would have a shorter overall survival time. The prognosis prediction significance of KIF21A was well validated by the joint-effect survival analysis, stratified survival analysis, and nomogram. Meanwhile, the gene set enrichment analysis and genome-wide co-expression analysis revealed that KIF21A might involve in DNA damage and repair, transcription and translation process, post-translation protein modification, cell cycle, carcinogensis genes and pathways. CONCLUSIONS: Our current research demonstrated that KIF21A could serve as a potential prognostic biomarker for patient with early-stage PDAC after pancreaticoduodenectomy.

Genome­wide investigation of the clinical implications and molecular mechanism of long noncoding RNA LINC00668 and protein­coding genes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of tumor­related mortalities worldwide. Long noncoding RNAs have been reported to be associated with tumor initiation, progression and prognosis. The present study aimed to explore the association between long noncoding RNA LINC00668 and its co­expression correlated protein­coding genes (PCGs) in HCC. Data of 370 HCC patients from The Cancer Genome Atlas database were used for analysis. LINC00668 and its top 10 PCGs were selected to determine their diagnostic and prognostic value. Molecular mechanisms were explored to identify metabolic processes that LINC00668 and its PCGs are involved in. Prognosis­related clinical factors and PCGs were used to construct a nomogram for predicting prognosis in HCC. A Connectivity Map was constructed to identify candidate target drugs for HCC. The top 10 PCGs identified were: Pyrimidineregic receptor P2Y4 (P2RY4), signal peptidase complex subunit 2 (SPCS2), family with sequence similarity 86 member C1 (FAM86C1), tudor domain containing 5 (TDRD5), ferritin light chain (FTL), stratifin (SFN), nucleolar complex associated 2 homolog (NOC2L), peroxiredoxin 1 (PRDX1), cancer/testis antigen 2 CTAG2 and leucine zipper and CTNNBIP1 domain containing (LZIC). FAM86C1, CTAG2 and SFN had significant diagnostic value for HCC (total area under the curve ≥0.7, P≤0.05); LINC00668, FAM86C1, TDRD5, FTL and SFN were of significant prognostic value for HCC (all P≤0.05). Investigation into the molecular mechanism indicated that LINC00668 affects cell division, cell cycle, mitotic nuclear division, and drug metabolism cytochrome P450 (all P≤0.05). The Connectivity Map identified seven candidate target drugs for the treatment of HCC, which were: Indolylheptylamine, mimosine, disopyramide, lidocaine, NU­1025, bumetanide, and DQNLAOWBTJPFKL­PKZXCIMASA­N (all P≤0.05). Our findings indicated that LINC00668 may function as an oncogene and its overexpression indicates poor prognosis of HCC. FAM86C1, CTAG2 and SFN are of diagnostic significance, while FAM86C1, TDRD5, FTL and SFN are of prognostic significance for HCC.