Composition regulates dissolved organic matter adsorption onto iron (oxy)hydroxides and its competition with phosphate: Implications for organic carbon and phosphorus immobilization in lakes.

Dissolved organic matter (DOM) is a heterogeneous pool of compounds and exhibits diverse adsorption characteristics with or without phosphorous (P) competition. The impacts of these factors on the burial and mobilization of organic carbon and P in aquatic ecosystems remain uncertain. In this study, an algae-derived DOM (ADOM) and a commercially available humic acid (HA) with distinct compositions were assessed for their adsorption behaviors onto iron (oxy)hydroxides (FeOx), both in the absence and presence of phosphate. ADOM contained less aromatics but more protein-like and highly unsaturated structures with oxygen compounds (HUSO) than HA. The adsorption capacity of FeOx was significantly greater for ADOM than for HA. Protein-like and HUSO compounds in ADOM and humic-like compounds and macromolecular aromatics in HA were preferentially adsorbed by FeOx. Moreover, ADOM demonstrated a stronger inhibitory effect on phosphate adsorption than HA. This observation suggests that the substantial release of autochthonous ADOM by algae could elevate internal P loading and pose challenges for the restoration of restore eutrophic lakes. The presence of phosphate suppressed the adsorption of protein-like compounds in ADOM onto FeOx, resulting in an increase in the relative abundance of protein-like compounds and a decrease in the relative abundance of humic-like compounds in post-adsorption ADOM. In contrast, phosphate exhibited no discernible impact on the compositional fractionation of HA. Collectively, our results show the source-composition characters of DOM influence the immobilization of both DOM and P in aquatic ecosystems through adsorption processes. The preferential adsorption of proteinaceous compounds within ADOM and aromatics within HA highlights the potential for the attachment with FeOx to diminish the original source-specific signatures of DOM, thereby contributing to the shared DOM characteristics observed across diverse aquatic environments.

Genome-wide identification of the TIFY gene family in tobacco and expression analysis in response to Ralstonia solanacearum infection.

The TIFY gene family plays an essential role in plant development and abiotic and biotic stress responses. In this study, genome-wide identification of TIFY members in tobacco and their expression pattern analysis in response to Ralstonia solanacearum infection were performed. A total of 33 TIFY genes were identified, including the TIFY, PPD, ZIM&ZML and JAZ subfamilies. Promoter analysis results indicated that a quantity of light-response, drought-response, SA-response and JA-response cis-elements exist in promoter regions. The TIFY gene family exhibited expansion and possessed gene redundancy resulting from tobacco ploidy change. In addition, most NtTIFYs equivalently expressed in roots, stems and leaves, while NtTIFY1, NtTIFY4, NtTIFY18 and NtTIFY30 preferentially expressed in roots. The JAZ III clade showed significant expression changes after inoculation with R. solanacearum, and the expression of NtTIFY7 in resistant varieties, compared with susceptible varieties, was more stably induced. Furthermore, NtTIFY7-silenced plants, compared with the control plants, were more susceptible to bacterial wilt. These results lay a foundation for exploring the evolutionary history of TIFY gene family and revealing gene function of NtTIFYs in tobacco bacterial wilt resistance.

Comprehensive genome sequence analysis of Ralstonia solanacearum gd-2, a phylotype I sequevar 15 strain collected from a tobacco bacterial phytopathogen.

Introduction: Plant bacterial wilt is an important worldwide disease caused by Ralstonia solanacearum which is a complex of species. Methods: In this study, we identified and sequenced the genome of R. solanacearum strain gd-2 isolated from tobacco. Results: Strain gd-2 was identified as R. solanacearum species complex (RSSC) phylotype I sequevar 15 and exhibited strong pathogenicity to tobacco. The genome size of gd-2 was 5.93 Mb, including the chromosomes (3.83 Mb) and the megaplasmid (2.10 Mb). Gene prediction results showed that 3,434 and 1,640 genes were identified in the chromosomes and plasmids, respectively. Comparative genomic analysis showed that gd-2 exhibited high conservation with ten highly similar strain genomes and the differences between gd-2 and other genomes were mainly located at positions GI12-GI14. 72 type III effectors (T3Es) were identified and RipAZ2 was a T3E specific to gd-2 compared with other eight sequenced strain. Discussion: Our study provides a new basis and evidence for studying the pathogenic mechanism of R. solanacearum.

Transcriptomics and virus-induced gene silencing identify defence-related genes during Ralstonia solanacearum infection in resistant and susceptible tobacco.

Bacterial wilt (BW) caused by Ralstonia solanacearum is a globally prevalent bacterial soil-borne disease. In this study, transcriptome sequencing were subjected to roots after infection with the R. solanacearum in the resistant and susceptible tobacco variety. DEGs that responded to R. solanacearum infection in both resistant and susceptible tobacco contributed to pectinase and peroxidase development and were enriched in plant hormone signal transduction, signal transduction and MAPK signalling pathway KEGG terms. Core DEGs in the resistant tobacco response to R. solanacearum infection were enriched in cell wall, membrane, abscisic acid and ethylene terms. qRT-PCR indicated that Nitab4.5_0004899g0110, Nitab4.5_0004234g0080 and Nitab4.5_0001439g0050 contributed to the response to R. solanacearum infection in different resistant and susceptible tobacco. Silencing the p450 gene Nitab4.5_0001439g0050 reduced tobacco resistance to bacterial wilt. These results improve our understanding of the molecular mechanism of BW resistance in tobacco and solanaceous plants.

Radiation Reaction and Gravitational Waves at Fourth Post-Minkowskian Order.

We obtain the total impulse in the scattering of nonspinning binaries in general relativity at fourth post-Minkowskian order, i.e., O(G^{4}), including linear, nonlinear, and hereditary radiation-reaction effects. We derive the total radiated spacetime momentum as well as the associated energy flux. The latter can be used to compute gravitational-wave observables for generic (un)bound orbits. We employ the ("in-in") Schwinger-Keldysh worldline effective field theory framework in combination with modern "multiloop" integration techniques from collider physics. The complete results are in agreement with various partial calculations in the post-Minkowskian and post-Newtonian expansion.

Stability of organic matter-iron-phosphate associations during abiotic reduction of iron.

The stability of organic matter-iron-phosphate (OM-Fe-P) association has an important impact on the migration and sequestration of organic carbon (OC) and P in the environment. Here, we examined the release characteristics of Fe, P and OM due to the abiotic reduction of OM-Fe-P associations by Na-dithionite. The associations were synthesized with algae-derived OM (AOM) and terrestrial humic acid (HA) through either adsorption onto iron (hydr)oxide or coprecipitation with Fe(III). Results indicated that OM and P adsorbed onto the associations were rapidly released, whereas coprecipitation yielded much lower release rates of Fe, P, and OM. The stronger inhibitory effect on reduction from coprecipitation can be explained by larger particles formed by coprecipitation and coprecipitation taking up more OC that had a passivation effect on the associations. The release rates of OM and P were lower in coprecipitates formed with HA than formed with AOM for a given OC/Fe ratio. This observation can be attributed to a patchy distribution of OC in AOM associated coprecipitates, which showed a weaker aggregation of OC with Fe and P. In contrast, the distribution of OC in HA-associated coprecipitates was more homogenous, enabling a stronger aggregation of OM with P and a greater passivation effect on P release. Our results revealed that OM sources, association formation pathways, and elemental stoichiometry collectively controlled the stability of OM-Fe-P associations.

Alterations in circadian rhythms aggravate Acetaminophen-induced liver injury in mice by influencing Acetaminophen metabolization and increasing intestinal permeability.

Acetaminophen (APAP) is the most common antipyretic and analgesic drug causing drug-induced liver injury (DILI). Alterations in circadian rhythms can adversely affect liver health, especially metabolic and detoxification functions. However, the effect of circadian rhythm alterations induced by environmental factors on APAP-induced liver injury and the underlying mechanisms are not well known. In this study, a mouse model of circadian rhythm alterations was established by light/dark cycle shift and then treated with excessive APAP. The liver injury indexes, APAP-related metabolic enzymes, and intestinal permeability in mice were evaluated by biochemical analysis, quantitative real-time PCR, enzyme-linked immunosorbent assays, and histopathology. Results showed that circadian rhythm alterations resulted in increased reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased liver superoxide dismutase (SOD), glutathione, and CYP1A2 and CYP3A11 mRNA expression, and increased serum diamine oxidase, lipopolysaccharide, and D-lactate in the mice. Compared with control mice, APAP induced higher serum alanine aminotransferase and aspartate aminotransferase, liver interleukin-1ß and tumor necrosis factor-α mRNA, ROS and MDA, lower SOD, glutathione, and UDP-glucuronosyltransferases /sulfotransferases mRNA and more severe liver necrosis and intestinal damage in mice with alterations in circadian rhythms. In conclusion, circadian rhythm alterations by light/dark cycle shift resulted in increased oxidative stress and intestinal permeability in the mice and exacerbated APAP-induced liver injury by influencing APAP metabolization and increasing intestinal permeability.

Increased Serum Pentraxin 3 Levels are Associated with Poor Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of liver-related mortality. Serum pentraxin 3 (PTX3) has been revealed to be associated with the development of hepatitis B virus (HBV)-related HCC. This study evaluated whether serum PTX3 is related to the survival of HBV-related HCC patients. METHODS: One hundred and seven patients with HBV-related HCC were included. Baseline serum PTX3 levels were quantified using quantitative immunoassay. The HCC patients were followed-up for a median of 24 months and divided into high serum PTX3 level and low PTX3 level groups according to the baseline serum PTX3 levels. The overall survivals of the HBV-related HCC patients according to the serum PTX3 levels were compared. Factors potentially influencing the prognosis of the patients with HBV-related HCC were analyzed. RESULTS: HCC patients with high serum PTX3 levels [PTX3 > 9.25ng/mL (n=85)] had a shorter overall survival time than HCC patients with low serum PTX3 levels [PTX3 ≤ 9.25ng/mL (n=22)] (P = 0.049). HCC patients with serum PTX3 levels between >9.25ng/mL and ≤9.25ng/mL had significant difference in HCC histology grade. Multivariate analysis showed that PTX3 level was an independent risk factor related to the overall survival of HCC patients (hazard ratio: 1.058, 95% confidence interval: 1.031-1.085, P <0.001). CONCLUSION: These results support the involvement of PTX3 in the disease progression of HCC and suggest the potential of using serum PTX3 levels as a biomarker for the prognostic prediction of HBV-related HCC patients.

A nomogram for discrimination of non-alcoholic fatty liver disease in patients with chronic hepatitis B.

OBJECTIVES: Comorbid of non-alcoholic fatty liver disease (NAFLD) in chronic hepatitis B (CHB) patients is common but no simple noninvasive diagnostic methods are available for the identification. This study aims to develop a noninvasive nomogram for accurate detection of NAFLD in CHB patients. PATIENTS AND METHODS: This study included 535 liver biopsy-proven CHB patients with or without comorbid NAFLD. Independent risk factors of NAFLD were identified by multivariate logistic regression analysis. The risk factors identified were then incorporated into the nomogram. Performance of the nomogram was assessed by calibration, receiver operating characteristic (ROC) curve and decision curve analysis. RESULTS: Of the 535 patients, 100 patients (18.69%) were diagnosed as CHB/NAFLD and 435 patients (81.31%) as simple CHB. Body mass index, serum uric acid and low-density lipoprotein cholesterol levels and diabetes mellitus were independent risk factors of NAFLD. The nomogram incorporating these 4 factors had an area under ROC curve (AUC) of 0.864, achieved good concordance index of 0.864 (95% confidence interval: 0.832-0.892) for predicting NAFLD in the patients and had well-fitted calibration curves. The nomogram had a significantly higher AUC than some previously reported models. The decision curve analysis yielded larger net benefit. CONCLUSION: This study developed a simple, noninvasive, effective and convenient nomogram that achieved an optimal detection of NAFLD in CHB patients. Using this nomogram, the risk for an individual patient to have NAFLD could be discriminated, leading to a rational clinical management.

Serum pentraxin 3 as a biomarker of hepatocellular carcinoma in chronic hepatitis B virus infection.

Biomarkers for early diagnosis of hepatocellular carcinoma (HCC) are needed in chronic hepatitis B virus (HBV) infection, a leading cause of HCC. We evaluated whether measurement of serum pentraxin 3 (PTX3) could improve diagnosis of HCC in chronic HBV infection. Data from patients with HBV-related chronic hepatitis (n = 159), cirrhosis (n = 99) and HCC (n = 107), and healthy controls (n = 151) were analyzed. Serum PTX3 concentration was measured by immunoassay. Area under the receiver operating characteristic curve (AUC) was applied to assess diagnostic accuracy. PTX3 levels were significantly higher in HBV patients than in healthy controls (P < 0.001) and in HCC than in chronic hepatitis (P < 0.001) or cirrhosis patients (P < 0.001). PTX3 was an independent risk factor of HCC [odds ratio (OR) 1.617, P < 0.001] and could distinguish HCC in chronic HBV infection [cutoff 9.231 ng/mL, AUC 0.929 with 95% confidence interval (CI) of 0.898-0.953], including α-fetoprotein (AFP) negative [cutoff 8.985 ng/mL, AUC (95%CI) 0.947 (0.908-0.973)] and early-stage HCC [cutoff 9.359 ng/mL, AUC (95%CI) 0.920 (0.885-0.947)]. Combination of PTX3 with AFP improved the discrimination of early HCC from chronic HBV infection [AUC (95%CI) 0.948 (0.918-0.970)]. In short, PTX3 measurement could identify HCC, including AFP-negative and early-stage HCC, in chronic HBV infection.

Involvement of NEK2 and its interaction with NDC80 and CEP250 in hepatocellular carcinoma.

BACKGROUND: NEK2 has an established involvement in hepatocellular carcinoma (HCC) but the roles of NEK2 and its interacting proteins in HCC have not been systematically explored. METHODS: This study examined NEK2 and its interacting proteins in HCC based on multiple databases. RESULTS: NEK2 mRNA was highly expressed in HCC tissues compared with normal liver tissues. The survival of HCC patients with high NEK2 mRNA expression was shorter than those with low expression. MAD1L1, CEP250, MAPK1, NDC80, PPP1CA, PPP1R2 and NEK11 were the interacting proteins of NEK2. Among them, NDC80 and CEP250 were the key interacting proteins of NEK2. Mitotic prometaphase may be the key pathway that NEK2 and its interacting proteins contributed to HCC pathogenesis. NEK2, NDC80 and CEP250 mRNAs were highly expressed in HCC tissues compared with normal liver tissues. The mRNA levels of NEK2 were positively correlated with those of NDC80 or CEP250. Univariate regression showed that NEK2, NDC80 and CEP250 mRNA expressions were significantly associated with HCC patients' survival. Multivariate regression showed that NDC80 mRNA expression was an independent predictor for HCC patients' survival. Methylations and genetic alterations of NEK2, NDC80 and CEP250 were observed in HCC samples. The alterations of NEK2, NDC80 and CEP250 genes were co-occurrence. Patients with high mRNA expression and genetic alterations of NEK2, NDC80 and CEP250 had poor prognosis. CONCLUSIONS: NEK2 and its interacting proteins NDC80 and CEP250 play important roles in HCC development and progression and thus may be potentially used as biomarkers and therapeutic targets of HCC.

Association of LIN28B polymorphisms with chronic hepatitis B virus infection.

BACKGROUND: LIN28B is involved in multiple cellular developmental processes, tissue inflammatory response and tumourigenesis. The association of LIN28B polymorphisms with hepatitis B virus (HBV) infection remains unknown. METHODS: This study investigated the association of LIN28B rs314277, rs314280, rs369065 and rs7759938 polymorphisms in patients with chronic HBV infection, a major cause of liver disease including hepatocellular carcinoma (HCC). A total of 781 individuals including 515 cases of chronic HBV infection (91 asymptomatic carrier status, 128 chronic hepatitis, 127 cirrhosis and 169 HCC), 97 HBV infection resolvers and 169 healthy controls were investigated. RESULTS: LIN28 rs314280 genotypes GA + AA were higher in resolver and controls than patients (P = 0.011). Patients had significantly lower rs314280 allele A than resolvers (P = 0.031, OR 0.689, 95%CI 0.491-0.969) or controls (P = 0.034, OR 0.741, 95%CI 0.561-0.978). In dominant model, patients had significantly lower rs314280 genotypes AA+GA than controls (P = 0.008, OR 0.623, 95%CI 0.439-0.884). LIN28 rs7759938 genotypes TC + CC were higher in resolvers and controls than patients (P = 0.015). Patients had significantly lower rs7759938 allele C than resolvers (P = 0.048, OR 0.708, 95%CI 0.503-0.999). In dominant model, patients had significantly lower rs7759938 genotypes TC + CC than controls (P = 0.010, OR 0.632, 95%CI 0.445-0.897). Chronic hepatitis patients had lower frequency of rs369065 genotype TC than asymptomatic carriers, cirrhosis and HCC (P = 0.019). CONCLUSIONS: These results suggest that LIN28 rs314280 and rs7759938 may be related to the susceptibility of chronic HBV infection. Further studies are warranted to examine the association of LIN28B polymorphisms with HBV-related diseases, especially HCC.

Circulating CTLA-4 levels and CTLA4 polymorphisms associate with disease condition and progression and hepatocellular carcinoma patients' survival in chronic hepatitis B virus infection.

BACKGROUND: CTLA-4 is involved in the immune dysfunction of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study analyzed the association of circulating CTLA-4 levels and CTLA4 polymorphisms with disease condition and progression in chronic HBV infection. METHODS: Serum CTLA-4 levels and CTLA4 rs231775 and rs5742909 polymorphisms were determined in patients with various HBV-related diseases [53 asymptomatic HBV carrier status (ASC), 147 chronic hepatitis, 130 cirrhosis and 102 HCC] and nearly a 10-year follow-up. RESULTS: Serum CTLA-4 levels were stepwisely increased from ASC, chronic hepatitis, cirrhosis to HCC and independently associated with HCC (OR 2.628, P < 0.001). HCC patients had lower frequencies of rs231775 genotype GA, genotype AA and allele A than ASC, chronic hepatitis and cirrhosis patients. Rs231775 genotype GG was independently associated with HCC (OR 2.324, P = 0.010) and higher CTLA-4 levels in patients with HBV infection. In the follow-up, higher baseline CTLA-4 levels and CTLA4 rs231775 genotype GG significantly associated with disease progression from chronic hepatitis to cirrhosis (OR 2.561, P = 0.011 and OR 2.799, P = 0.015, respectively) or from cirrhosis to HCC (OR 2.673, P = 0.008 and OR 2.097, P = 0.023, respectively) and with a shorter overall survival in HCC patients (HR 0.317, P = 0.018 and HR 0.682, P = 0.026, respectively). Rs5742909 had no significant association with CTLA-4 levels and disease progression. CONCLUSION: CTLA-4 levels and CTLA4 rs231775 polymorphism associate with the disease condition and progression and HCC development in chronic HBV infection and their determination may be used for monitoring disease progression and predicting patient prognosis.

Genetic association of polymorphisms at the intergenic region between PRDM1 and ATG5 with hepatitis B virus infection in Han Chinese patients.

Chronic hepatitis B virus (HBV) infection is related to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), and the interplay between the virus and host immune response leads to different outcomes of the infection. PR domain zinc finger protein 1 (PRDM1) and autophagy-related protein 5 (ATG5) are involved in immune response and HBV infection. An intergenic region between PRDM1 and ATG5 (PRDM1-ATG5 region) has been identified, and single-nucleotide polymorphisms (SNPs) in this region were shown to be involved in immune regulation. This study investigated the functionally relevant rs548234, rs6937876, and rs6568431 polymorphisms at the PRDM1-ATG5 region in a Han Chinese population (403 patients with chronic HBV infection [171 chronic hepatitis, 119 cirrhosis, and 113 HCC], 70 infection resolvers, and 196 healthy controls). The frequencies of the rs6568431 allele A in HBV patients (P = .005) and genotype CA in infection resolvers (P = .005) were significantly higher than in healthy controls. In the dominant model, HCC patients had significantly higher frequencies of rs548234 genotypes CC + TC than cirrhosis patients (P = .009). Rs548234 was an independent factor for HCC in comparison with either cirrhosis (P = .005) or all chronic HBV infection without HCC (P = .018). Functional annotation showed evidence of the role of the SNPs in gene regulation. In conclusion, through this study it is revealed for the first time that rs6568431 may be associated with susceptibility to HBV infection and that rs548234 may be associated with HCC risk in chronic HBV infection, supporting the presence of HBV-related disease-causing regulatory polymorphisms in the PRDM1-ATG5 intergenic region.

PRDM1 rs1010273 polymorphism is associated with overall survival of patients with hepatitis B virus-related hepatocellular carcinoma.

T cell exhaustion is involved in the pathogenesis of chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). B lymphocyte-induced maturation protein 1 (BLIMP-1), encoded by the PRDM1 gene, plays a crucial role in T cell exhaustion. This study investigated PRDM1 rs1010273 and rs2185379 polymorphisms in 403 patients with chronic HBV infection (171 chronic hepatitis, 119 liver cirrhosis and 113 HCC), 70 spontaneous HBV infection resolvers and 196 healthy controls. The results showed that the rs1010273 and rs2185379 polymorphisms had no significant differences between patients with chronic HBV infection and healthy controls or between patients with different clinical diseases. However, PRDM1 rs1010273 polymorphism was shown to be significantly associated with the overall survival of patients with HBV-related HCC. The 1-, 3-, and 5-year survival rates of HCC patients were 70.5%, 34.6%, and 11.5%, respectively, in genotype GG carriers and 91.4%, 51.4% and 31.4%, respectively, in genotypes AA + GA carriers (p =  0.008). Multivariate analysis showed that PRDM1 rs1010273 polymorphism was an independent factor associated with the overall survival of patients with HCC (odds ratio, 0.529; 95% confidence interval, 0.126-0.862; p =  0.002). These results provide novel evidence for a role of PRDM1 rs1010273 in the pathogenesis of HBV-related HCC. Additional studies are needed to replicate and extend the findings of this study and to elucidate the underlying mechanisms.

PRDM1 levels are associated with clinical diseases in chronic HBV infection and survival of patients with HBV-related hepatocellular carcinoma.

PR domain zinc finger protein 1 (PRDM1)/B lymphocyte-induced maturation protein 1 (BLIMP1) is a transcriptional repressor involved in B and T cell responses which are implicated in chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study investigated the association of PRDM1 with clinical diseases of chronic HBV infection and prognosis of HBV -related HCC patients. Serum PRDM1 levels were determined in 403 patients with chronic HBV infection (171 chronic hepatitis, 119 cirrhosis and 113 HCC), 70 HBV infection resolvers and 96 healthy control individuals. The PRDM1 levels were analyzed with regard to clinical diseases and overall survival of HCC patients. Serum PRDM1 concentrations in patients with chronic HBV infection were significantly elevated compared with infection resolvers and healthy controls. HBV-related HCC patients had the most significantly elevated PRDM1 levels. PRDM1 levels could considerably differentiate HCC from chronic hepatitis [area under receiver operating characteristic curve (AUC) 0.889, p < 0.001] or cirrhosis (AUC 0.910, p < 0.001). HCC patients with high PRDM1 levels had a poor prognosis (>300 pg/mL vs. ≤300 pg/mL, p = 0.001). High PRDM1 levels were independently associated with increased mortality in HCC patients (hazard ratio 2.997, 95% confidence interval 1.103-4.722, p = 0.003). Overall, this study demonstrated that PRDM1 levels are associated with the clinical diseases of chronic HBV infection. Highly elevated PRDM1 levels are discriminative of HCC from other clinical diseases and indicative of a poor prognosis of HCC patients. The potential association of PRDM1 levels with disease progression and treatment response warrants further investigation.

Genetic association and interaction of PD1 and TIM3 polymorphisms in susceptibility of chronic hepatitis B virus infection and hepatocarcinogenesis.

The PD1 (rs2227982, rs41386349, rs6710479, rs7421861, and rs7565639) and TIM3 (rs11134551, rs11742259, rs246871, rs25855, and rs31223) polymorphisms were examined in 362 patients with chronic hepatitis B virus (HBV) infection, 91 HBV infection resolvers, and 158 healthy controls. Univariate logistic regression was carried out by SNPstats to detect the associations. Multifactor dimensionality reduction (MDR) analysis was performed to explore interactions between PD1 and TIM3 polymorphisms. Associations of polymorphisms with clinical disease were also evaluated. Compared with patients with chronic HBV infection and healthy controls, HBV infection resolvers had a lower frequency of PD1 rs41386349 allele A, higher frequency of PD1 rs6710479 allele C, and higher frequency of TIM3 rs246871 genotypes TC and TC + CC. A best MDR model composed of PD1 rs2227982, rs41386349, and rs7421861, and TIM3 rs11134551, rs11742259, rs246871, rs25855, and rs31223 was observed between patients with chronic HBV infection and HBV infection resolvers (maximum testing balance accuracy, 0.5803; maximum cross-validation consistency, 9/10; P = 0.0010). PD1 rs2227982, rs6710479, and rs7421861 were associated with a higher hepatocellular carcinoma risk. These findings suggest that PD1 rs41386349 and rs6710479 and TIM3 rs246871 and interactions between PD1 and TIM3 polymorphisms may affect the susceptibility of chronic HBV infection and PD1 rs2227982, rs6710479, and rs7421861 may implicate in hepatocarcinogenesis.

Autophagy-Related 5 Gene rs510432 Polymorphism Is Associated with Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Virus Infection.

BACKGROUND: Despite the identification of autophagy-related protein 5 (ATG5) as a molecule involved in the activated autophagy machinery during hepatitis B virus (HBV) infection and hepatocarcinogenesis, the consequences of ATG5 mutation carriage for patients with chronic HBV infection remain unclear. This study examined the association of ATG5 polymorphisms with HBV-related diseases including hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Two functionally relevant polymorphisms ATG5 rs573775 and rs510432 were genotyped by ligase detection reaction-polymerase chain reaction in 403 patients with chronic HBV infection (171 chronic hepatitis, 119 cirrhosis and 113 HCC) and 196 healthy controls. Univariate and multivariate logistic regression was performed to evaluate factors associated with HCC. RESULTS: The rs573775 genotype and allele frequencies had no significant differences between patients with different clinical diseases. However, HCC patients had significantly higher frequency of rs510432 genotype AA (odds ratio [OR] 2.185, 95% confidence interval [CI] 1.042-4.581, P = 0.037, P value by Bonferroni correction [Pc] = 0.074) and allele A (OR 1.435, 95% CI 1.023-2.013, Pc = 0.036) than chronic hepatitis patients. In multivariate analyses, rs510432 allele A-containing genotypes (AA+GA) were independently associated with cirrhosis in comparison to chronic hepatitis (OR 1.927, 95%CI 1.011-3.017, P = 0.032). The rs510432 genotypes AA+GA were also independently associated with HCC in comparison to chronic hepatitis (OR 2.583, 95% CI 1.025-3.911, P = 0.006) or chronic HBV infection without HCC (OR 2.632, 95% CI 1.067-3.482, P = 0.032). CONCLUSION: These results indicate that rs510432 genotypes AA+GA are associated with disease progression and HCC risk in chronic HBV infection, providing novel evidence for a role of ATG5 in the pathogenesis of HBV-related HCC. ABBREVIATIONS: HBV: hepatitis B virus; HCC hepatocellular carcinoma; TNFSF10: tumor necrosis factor superfamily member 10; ATG5: autophagy-related protein 5; DNA: deoxyribonucleic acid; LDR-PCR: ligase detection reactions-polymerase chain reaction; PCR: polymerase chain reaction; SLE: systemic lupus erythematosus; BD: Behçet's disease; IL-10: interlukin-10; LPS: lipopolysaccharide; PBMC: peripheral blood mononuclear cells; CWP: coal workers' pneumoconiosis; TNF-α: tumor necrosis factor-α.

Composition of dissolved organic matter controls interactions with La and Al ions: Implications for phosphorus immobilization in eutrophic lakes.

Applications of aluminium (Al) salt or lanthanum (La) modified bentonite (LMB) have become popular methodologies for immobilizing phosphorus (P) in eutrophic lakes. The presence of humic substances, has been shown to inhibit this form of treatment due to the complexation with La/Al. However, the effects of other dissolved organic matter (DOM), especially that derived from phytoplankton (the dominant source in eutrophic lakes) are unknown. In this study, the interaction with La/Al of Suwannee River Standard Humic Acid Standard II (SRHA) and algae-derived DOM (ADOM) were investigated and compared. Differed to SRHA which was dominated by polyphenol-like component (76.8%, C1-SRHA), majority in ADOM were protein-like substance, including 41.9% tryptophan-like component (C2-ADOM) and 21.0% tyrosine-like component (C3-ADOM). Two reactions of complexation and coprecipitation were observed between SRHA/ADOM and La/Al. Complexation dominated at low metal inputs less than 10 µM and coprecipitation was the main reaction at higher metal inputs. For ADOM, the tryptophan-like component (C2-ADOM) was the important component to react with metal. The reaction rate for C2-ADOM with La were about two-third of that for C1-SRHA, indicating that the influence of C2-ADOM was significant during the P immobilization by La/Al-based treatment in eutrophic lakes. The P removal data in the presence of ADOM confirmed the significant inhibition of ADOM. In addition, based on the composition of coprecipitates and relatively biodegradable character of tryptophan-like substances (C2-ADOM), the coprecipitation of ADOM was assumed to reduce the stability of precipitated P in eutrophic lakes. The release of P from the potential biodegradation of the coprecipitates and thus the possible decline of the performance of P immobilization by La/Al-based treatments is an important work in the future.

Bioinformatics Analysis based on Multiple Databases Identifies Hub Genes Associated with Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common liver cancer and the mechanisms of hepatocarcinogenesis remain elusive. OBJECTIVE: This study aims to mine hub genes associated with HCC using multiple databases. METHODS: Data sets GSE45267, GSE60502, GSE74656 were downloaded from GEO database. Differentially expressed genes (DEGs) between HCC and control in each set were identified by limma software. The GO term and KEGG pathway enrichment of the DEGs aggregated in the datasets (aggregated DEGs) were analyzed using DAVID and KOBAS 3.0 databases. Protein-protein interaction (PPI) network of the aggregated DEGs was constructed using STRING database. GSEA software was used to verify the biological process. Association between hub genes and HCC prognosis was analyzed using patients' information from TCGA database by survminer R package. RESULTS: From GSE45267, GSE60502 and GSE74656, 7583, 2349, and 553 DEGs were identified respectively. A total of 221 aggregated DEGs, which were mainly enriched in 109 GO terms and 29 KEGG pathways, were identified. Cell cycle phase, mitotic cell cycle, cell division, nuclear division and mitosis were the most significant GO terms. Metabolic pathways, cell cycle, chemical carcinogenesis, retinol metabolism and fatty acid degradation were the main KEGG pathways. Nine hub genes (TOP2A, NDC80, CDK1, CCNB1, KIF11, BUB1, CCNB2, CCNA2 and TTK) were selected by PPI network and all of them were associated with prognosis of HCC patients. CONCLUSION: TOP2A, NDC80, CDK1, CCNB1, KIF11, BUB1, CCNB2, CCNA2 and TTK were hub genes in HCC, which may be potential biomarkers of HCC and targets of HCC therapy.