Neutral lysophosphatidylcholine mediates α-synuclein-induced synaptic vesicle clustering.

α-synuclein (α-Syn) is a presynaptic protein that is involved in Parkinson's and other neurodegenerative diseases and binds to negatively charged phospholipids. Previously, we reported that α-Syn clusters synthetic proteoliposomes that mimic synaptic vesicles. This vesicle-clustering activity depends on a specific interaction of α-Syn with anionic phospholipids. Here, we report that α-Syn surprisingly also interacts with the neutral phospholipid lysophosphatidylcholine (lysoPC). Even in the absence of anionic lipids, lysoPC facilitates α-Syn-induced vesicle clustering but has no effect on Ca2+-triggered fusion in a single vesicle-vesicle fusion assay. The A30P mutant of α-Syn that causes familial Parkinson disease has a reduced affinity to lysoPC and does not induce vesicle clustering. Taken together, the α-Syn-lysoPC interaction may play a role in α-Syn function.

Wild-type α-synuclein inherits the structure and exacerbated neuropathology of E46K mutant fibril strain by cross-seeding.

Heterozygous point mutations of α-synuclein (α-syn) have been linked to the early onset and rapid progression of familial Parkinson's diseases (fPD). However, the interplay between hereditary mutant and wild-type (WT) α-syn and its role in the exacerbated pathology of α-syn in fPD progression are poorly understood. Here, we find that WT mice inoculated with the human E46K mutant α-syn fibril (hE46K) strain develop early-onset motor deficit and morphologically different α-syn aggregation compared with those inoculated with the human WT fibril (hWT) strain. By using cryo-electron microscopy, we reveal at the near-atomic level that the hE46K strain induces both human and mouse WT α-syn monomers to form the fibril structure of the hE46K strain. Moreover, the induced hWT strain inherits most of the pathological traits of the hE46K strain as well. Our work suggests that the structural and pathological features of mutant strains could be propagated by the WT α-syn in such a way that the mutant pathology would be amplified in fPD.

Multi-omics network analysis on samples from sequential biopsies reveals vital role of proliferation arrest for Macrosteatosis related graft failure in rats after liver transplantation.

To investigate the molecular impact of graft MaS on post-transplant prognosis, based on multi-omics integrative analysis. Rats were fed by methionine-choline deficient diet (MCD) for MaS grafts. Samples were collected from grafts by sequential biopsies. Transcriptomic and metabolomic profilings were assayed. Post-transplant MaS status showed a close association with graft failure. Differentially expressed genes (DEGs) for in-vivo MaS were mainly enriched on pathways of cell cycle and DNA replication. Post-transplant MaS caused arrests of graft regeneration via inhibiting the E2F1 centered network, which was confirmed by an in vitro experiment. Data from metabolomics assays found insufficient serine/creatine which is located on one­carbon metabolism was responsible for MaS-related GF. Pre-transplant MaS caused severe fibrosis in long-term survivors. DEGs for grafts from long-term survivors with pre-transplant MaS were mainly enriched in pathways of ECM-receptor interaction and focal adhesion. Transcriptional regulatory network analysis confirmed SOX9 as a key transcription factor (TF) for MaS-related fibrosis. Metabolomic assays found elevation of aromatic amino acid (AAA) was a major feature of fibrosis in long-term survivors. Graft MaS in vivo increased post-transplant GF via negative regulations on graft regeneration. Pre-transplant MaS induced severe fibrosis in long-term survivors via activations on ECM-receptor interaction and AAA metabolism.

Human health ambient water quality criteria and risk assessment of pentachlorophenol in Poyang Lake Basin, China.

Pentachlorophenol (PCP) has been widely used as an insecticide for killing oncomelania (the intermediate host of schistosome) in China and leads to severe environmental contamination. Poyang Lake, as the largest freshwater lake and bird habitat in China, was once a schistosomiasis epidemic area. In this study, the concentrations of PCP in water and aquatic products from Poyang Lake were determined and analyzed, and then the human health ambient water quality criteria (AWQC) was derived based on native parameters of Poyang Lake basin. Finally, a comprehensive analysis of the health risks of drinking water and different types of aquatic products consumption was carried out. The results showed that PCP concentrations were ranged from 0.01 to 0.43 µg/L in surface water and 3.90 to 85.95 µg/kg in aquatic products. Due to the carcinogenicity of PCP, the human health AWQC for PCP are 0.02 µg/L for consumption of water and organisms and 0.03 µg/L for consumption of organisms only. Deterministic and probabilistic risk analysis indicated that the non-carcinogenic risk of PCP were acceptable in Poyang Lake, while the carcinogenic risk cannot be ignored. The health risks of PCP caused by aquatic products consumption were higher than that by drinking water. The percentages of acceptable risk for the population in Poyang Lake Basin were 99.95% at acceptable level of 10-4. Based on the sensitivity analysis, the impact of PCP concentrations on health risk values ranged from 53 to 82%. The study provided valuable information for regional water quality criteria development and water quality assessment.

Pressure Induced Clathrate Hydrogen-Rich Superconductors KH20 and KH30.

Hydrogen-rich compounds have long been considered as one of the hotspot materials for achieving room-temperature superconductivity. We systematically investigate the high-pressure phase diagram of the K-H system and identified two unreported clathrate extreme superhydrides KH20 and KH30, hosting high superconducting transition temperatures (Tc) of 283 and 243 K at 500 GPa, respectively. The extremely high hydrogen content significantly increases H-derived electronic density of states at the Fermi level, constituting the main contributor to participate in electron-phonon coupling thus producing high-Tc. The large electron localizations in the interstitial region of the metal lattice under high pressure effectively assist the dissociation of hydrogen molecular units, forming unique H36 cages. These results offer key insights into the stability and potential high-Tc superconductivity of compressed extreme superhydrides and will further stimulate related research.

Multistep Dissociation of Fluorine Molecules under Extreme Compression.

All elements that form diatomic molecules, such as H_{2}, N_{2}, O_{2}, Cl_{2}, Br_{2}, and I_{2}, are destined to become atomic solids under sufficiently high pressure. However, as revealed by many experimental and theoretical studies, these elements show very different propensity and transition paths due to the balance of reduced volume, lone pair electrons, and interatomic bonds. The study of F under pressure can illuminate this intricate behavior since F, owing to its unique position on the periodic table, can be compared with H, with N and O, and also with other halogens. Nevertheless, F remains the only element whose solid structure evolution under pressure has not been thoroughly studied. Using a large-scale crystal structure search method based on first principles calculations, we find that, before reaching an atomic phase, F solid transforms first into a structure consisting of F_{2} molecules and F polymer chains and then into a structure consisting of F polymer chains and F atoms, a distinctive evolution with pressure that has not been seen in any other elements. Both intermediate structures are found to be metallic and become superconducting, a result that adds F to the elemental superconductors.

Ammonia spatiotemporal distribution and risk assessment for freshwater species in aquatic ecosystem in China.

Ammonia has been of concern for its high toxicity to aquatic species and frequent detection in waters worldwide. This study calculated the national aquatic life criteria for ammonia in China. The temporal and spatial distributions were investigated and the multi-tier ecological risks were assessed for ammonia and un-ionized ammonia (NH3) during 2014-2018 based on a total of 18989 ammonia monitoring data from 110 monitoring sites in seven river basins. The sensitivity comparison of different species taxa to ammonia showed that Perciformes fish should be listed as a priority protected species in the derivation of ammonia criteria. The participation of introduced aquaculture species have no significant impact on the final criteria values (t-test, p > 0.05). The final criterion maximum concentration (CMC) and criterion continuous concentration (CCC) were 10.24 and 3.31 mg/L for ammonia (pH 7.0 and 20 °C). The interannual variation showed that decreasing trends were observed for ammonia and NH3 pollutions in the past five years. However, the increasing trends were observed for ammonia in Liao River basin, for NH3 in Yangtze River and Pearl River basins (2014-2018). The significant seasonal and geographical differences of ammonia and NH3 pollution were found. Moreover, the pollutions of ammonia and NH3 in some monitoring points of Huai River, Yellow River and Songhua River basins at the provincial borders were significant. The result of ecological risk assessment showed that the average exceedance probability for 5% affected species by NH3 in long-term exposure was 28.96% in the past five years.

Effects of acute ammonia toxicity on oxidative stress, DNA damage and apoptosis in digestive gland and gill of Asian clam (Corbicula fluminea).

Ammonia is one of the major pollutants associated with the main river basins due to ammonification of uneaten food and animal excretion, which usually brings detrimental health effects to aquatic invertebrate. However, the mechanisms of ammonia toxicity in aquatic invertebrate have rarely been reported. In this study, C. fluminea was exposed to different levels of ammonia (control group, 10 mg/L, and 25 mg/L) for 24 h and 48 h, and digestive gland and gill were collected to explore toxic effects on oxidative stress, DNA damage and apoptosis under ammonia stress. The results showed that ammonia poisoning could increase the activity of oxidative stress enzyme (SOD and CAT), inducing differentially expressed genes (DRAM2, GADD45, P53, BAX, BCL2, CASP8, CASP9, CASP3, HSP70 and HSP90) and different cytokines (IL-1 beta, IL-8, IL-17 and TNF-alpha) of DNA damage and apoptosis. The difference of toxic effects induced by ammonia among digestive gland and gill were also observed by real-time PCR and TUNEL staining. Our results will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in C. fluminea.

TCSBN: a database of tissue and cancer specific biological networks.

Biological networks provide new opportunities for understanding the cellular biology in both health and disease states. We generated tissue specific integrated networks (INs) for liver, muscle and adipose tissues by integrating metabolic, regulatory and protein-protein interaction networks. We also generated human co-expression networks (CNs) for 46 normal tissues and 17 cancers to explore the functional relationships between genes as well as their relationships with biological functions, and investigate the overlap between functional and physical interactions provided by CNs and INs, respectively. These networks can be employed in the analysis of omics data, provide detailed insight into disease mechanisms by identifying the key biological components and eventually can be used in the development of efficient treatment strategies. Moreover, comparative analysis of the networks may allow for the identification of tissue-specific targets that can be used in the development of drugs with the minimum toxic effect to other human tissues. These context-specific INs and CNs are presented in an interactive website http://inetmodels.com without any limitation.

Antioxidative enzyme activities in the Rhodeinae sinensis Gunther and Macrobrachium nipponense and multi-endpoint assessment under tonalide exposure.

Tonalide or acetyl hexamethyl tetralin (AHTN) is used as a fragrance additive in various household products. Recently, AHTN has drawn attention owing to its negative health effects on aquatic organisms. Data on AHTN toxicity toward aquatic species are limited. Therefore, this study tested the oxidative stress induced by AHTN exposure on the Rhodeinae sinensis Gunther and Macrobrachium nipponense. In this study, malonaldehyde (MDA) content and the activities of acetyl cholinesterase (AchE), superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase (CAT) in R. sinensis Gunther were tested after 30 days of exposure to 30.093, 34.005, 38.426, 43.421, 49.067, 55.444, 62.652, 70.800, and 80.000 µg/L AHTN, respectively. The MDA, AchE, SOD, GST and CAT in M. nipponense were tested after 40 days of exposure to 60.000, 72.000, 86.400, 103.680, 124.416, 149.299, 179.159, 214.991, and 257.989 µg/L AHTN, respectively. In addition, an integrated biomarker response (IBR) index was utilised to evaluate the integrated toxic effects of AHTN on R. sinensis Gunther and M. nipponense. Finally, the predicted no-effect concentrations (PNECs) of AHTN, based on reproduction, biochemistry, survival, chronic toxicity, and acute toxicity endpoints were derived. The results indicated that low concentrations of AHTN can induce significant changes of oxidative stress biomarkers. The no observed effect concentrations (NOECs) of SOD, GST, AchE, CAT, and MDA were 103.680, 72.000, <60.000, 72.000, and <60.000 µg/L for R. sinensis Gunther and 38.426, 43.421, 30.093, 30.093, and 38.426 µg/L for M. nipponense, respectively. The IBR calculation results showed that 149.299 µg/L AHTN caused the highest toxic effect on R. sinensis Gunther after 30 days of exposure, whereas 70.797 µg/L AHTN caused the greatest damage to M. nipponense after 40 days of exposure. The PNECs of AHTN based on the non-traditional endpoints of biochemistry and reproduction were 0.00145 µg/L and 0.000395 µg/L, respectively, which were significantly lower than the PNEC of 2.636 µg/L for traditional endpoint survival. Therefore, the protection of aquatic organisms based on non-traditional toxicity endpoints should be considered in ecological risk assessment.

Development of aquatic life criteria for tonalide (AHTN) and the ecological risk assessment.

AHTN (tonalide) is a polycyclic musk that is widely used as fragrance additive in numerous consumer products. AHTN is of great worldwide concern owing to its adverse effects on aquatic organisms and frequent detection in both domestic and foreign aquatic environments. Therefore, derivation of the aquatic life criteria for AHTN exposure is urgently needed. In this work, AHTN toxicity data for eight Chinese native freshwater organisms were used to derive a criterion maximum concentration of 59.39 µg/L and a criterion continuous concentration of 22.43 µg/L using United States Environmental Protection Agency guidelines. Toxicity tests showed that the annelid L. hoffmeisteri and the amphibian R. nigromaculata were the least and most sensitive species to AHTN, respectively. The sensitivity of the planktonic crustacean D. magna to AHTN obviously differed from that of the benthic crustacean M. nipponense. The AHTN and HHCB correlation analysis exhibited a strong positive linear correlation (R2 = 0.8622) in water. The ecological risk assessment showed that AHTN and HHCB posed a higher risk in foreign surface waters than Chinese waters, but a lower risk in foreign wastewater treatment plant effluent than in China. The ecological risks of AHTN and HHCB in most surveyed water bodies of various countries were at acceptable levels, with a few exceptions.

Aquatic life criteria derivation and ecological risk assessment of DEET in China.

N,N-diethyl-meta-toluamide (DEET) is the most widely used active ingredient in commercial insect repellents. In addition to its adverse effects in insects, DEET can affect non-target organisms in surface water systems. Nevertheless, the aquatic life criteria of DEET are not available. This study conducted both acute and chronic toxicity tests on DEET in native Chinese aquatic species, and derived its criterion maximum concentration (CMC) and criterion continuous concentration (CCC). The determined CMC and CCC of DEET were 21.53 and 0.52 mg/L, respectively. The toxicity data indicated that DEET exposure posed a higher toxicity to some algae than other aquatic species. Compared with other insect repellents, DEET exposure posed a moderate toxicity to aquatic species. Therefore, the exposure concentration of DEET in Chinese surface water was collected to assess the potential ecological risk. The preliminary ecological risk assessment showed that DEET posed negligible risk to aquatic ecosystems in China. However, considering its toxic effects on the growth and reproduction to aquatic organisms, the ecological risk posed by DEET is worth further concern.

Pyruvate kinase L/R is a regulator of lipid metabolism and mitochondrial function.

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) has been associated with altered expression of liver-specific genes including pyruvate kinase liver and red blood cell (PKLR), patatin-like phospholipase domain containing 3 (PNPLA3) and proprotein convertase subtilisin/kexin type 9 (PCSK9). Here, we inhibited and overexpressed the expression of these three genes in HepG2 cells, generated RNA-seq data before and after perturbation and revealed the altered global biological functions with the modulation of these genes using integrated network (IN) analysis. We found that modulation of these genes effects the total triglycerides levels within the cells and viability of the cells. Next, we generated IN for HepG2 cells, identified reporter transcription factors based on IN and found that the modulation of these genes affects key metabolic pathways associated with lipid metabolism (steroid biosynthesis, PPAR signalling pathway, fatty acid synthesis and oxidation) and cancer development (DNA replication, cell cycle and p53 signalling) involved in the progression of NAFLD and HCC. Finally, we observed that inhibition of PKLR lead to decreased glucose uptake and decreased mitochondrial activity in HepG2 cells. Hence, our systems level analysis indicated that PKLR can be targeted for development efficient treatment strategy for NAFLD and HCC.

Exposure and ecological risk of phthalate esters in the Taihu Lake basin, China.

The environmental spatial distribution and exposure risk of 6 phthalate esters (PAEs) including dimethyl phthalate (DMP), diethyl phthalate (DEP), butyl benzyl phthalate (BBP), di-n-octyl phthalate (DnOP), bis(2-ethylhexyl) phthalate (DEHP), and dibutyl phthalate (DBP), in surface water and sediment of Taihu Lake basin, China, were investigated at 65 sites. The exposure concentrations of 6 PAEs (∑6PAEs) detected in the samples spanned a range of 0.740-13.0 µg/L in surface water and 5.15-20.9 mg/kg in sediment. DBP and DEHP were the predominant compounds in surface water, with mean concentrations of 1.59 µg/L and 1.29 µg/L, respectively. DnOP was the predominant compound in sediment with mean concentration of 7.41 mg/kg. Ecological risk assessment was conducted by the hazard quotient method in which the predicted no effect concentration (PNEC) was derived from the species sensitivity distribution (SSD) curve. The results showed that DEHP in water phase posed a higher environmental risk than the other PAEs, while the DEP in sediment posed a high risk to the aquatic system. The study contributed to better understanding the presence of PAEs in Taihu Lake basin and provided valuable information for managing and controlling PAEs pollution.

Network analyses identify liver-specific targets for treating liver diseases.

We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co-expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver-specific genes co-expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver-specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver-specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin-like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.

Genome-Wide Association Study of MKI67 Expression and its Clinical Implications in HBV-Related Hepatocellular Carcinoma in Southern China.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a common malignant tumor with a high rate of recurrence. Immunohistochemical analysis of the marker of proliferation Ki-67 (MKI67) is used to assess proliferation activity of HCC The regulation of MKI67 expression remains unclear in HCC This study aims to explore the association between MKI67 expression and gene variants. METHODS: A total of 195 hepatitis B virus (HBV)-related HCC patients were genotyped using Illumina HumanExome BeadChip-12-1_A (242,901 markers). An independent cohort (97 subjects) validated the association of polymorphism determinants and candidate genes with MKI67 expression. The relationships between MKI67 with p53 and variants of candidate genes in the clinical outcomes of HCC patients were analyzed. RESULTS: We found that MKI67 combined with p53 was associated with a 3-year recurrence-free survival and five variants near TTN and CCDC8 were associated with MKI67 expression. TTN harboring rs2288563-TT and rs2562832-AA+CA indicated a favorable outcome for HCC patients. CONCLUSION: Variants near TTN and CCDC8 were associated with MKI67 expression, and rs2288563 and rs2562832 in TTN are potential biomarkers for the prediction of clinical outcomes in HBV-related HCC patients.

pH-dependent ecological risk assessment of pentachlorophenol in Taihu Lake and Liaohe River.

Pentachlorophenol (PCP) has been reported toxic to aquatic organisms, and it frequently occurs at relatively high concentrations in most Chinese waters due to the re-emergence of schistosomiasis since 2003. Several studies about Water Quality Criteria (WQC) for PCP had been performed to protect the aquatic ecosystem, but in most of these studies the toxicity data were not properly analyzed (e.g. screening and processing methods). Moreover, little study was carried out on the ecological risk assessment (ERA) based on environmental factors. In this study, through collecting published native toxicity data of PCP along with relationships between toxicity and pH, pH-dependent WQC was established using a standardized scientific statistical method in China. The Criterion Maximum Concentration (CMC) and Criterion Continuous Concentration (CCC) were expressed as a function of pH. These were (1) CMC = exp(1.361×pH-8.034) and (2) CCC = exp(1.361×pH-10.434). At pH 7.8, the derived CMC and CCC were 13.21 and 1.20µg/L, respectively. In addition, four tiers of the ERA were conducted based on pH for different waterbodies at different seasons. In tiered 1, 2, 3 and 4 ERA, PCP exposure concentrations were standardized to that at pH 7.8. Results showed that all levels of ERA method in the tiered framework were consistent with each other, and the risks of PCP in Liaohe river of wet season, Taihu lake and Liaohe river of dry season increased successively. The Hazard quotient (HQ) method indicated that small fluctuations in pH would lead to misleading hazard results. PCP concentrations of 8.66µg/L at pH 7.37 in one site posed more risk than PCP of 9.57µg/L at pH 7.93 in another site. The joint probability suggested that ecological risks may exist 11.84% in the dry season and 1.51% in the wet season in Liaohe River, and 4.98% in Taihu Lake, respectively while 5% thresholds (HC5) were set up to protect aquatic organisms. We hope this work could provide more information to manage and control PCP pollution in Taihe Lake and Liaohe River.

Spatial and temporal ecological risk assessment of unionized ammonia nitrogen in Tai Lake, China (2004-2015).

Ammonia toxicity varies largely due to its pH- and temperature-dependent speciation (unionized ammonia nitrogen, NH3-N). The seasonal and long-term trend of ammonia risk in ecologically significant sections of Tai Lake, China was unknown. In this study, a two-level (deterministic and quantitative) method was developed to assess the special ecological risks posed by NH3-N at 37 sites during two seasons (February and September) of 2014 in Tai Lake. The long-term temporal (2004-2015) risk posed by NH3-N was also assessed by comparing annual quantitative risk values (probability of exceeding acute or chronic threshold values) in three key sections of Tai Lake. The results indicated the species living in the Tai Lake were at a 0.04% and 32.45% chance of risk due to acute exposure, and a 1.97% and 92.05% chance of risk due to chronic exposure in February and September of 2014, respectively. Alarmingly, the chronic ecological risks of NH3-N in the Lanshanzui section of the Tai Lake remained >30% from 2004 to 2011. The chronic risk of NH3-N in all three key sections of Tai Lake started to decrease in 2011. This was likely the consequence of the control practice of eutrophication implemented in the Tai Lake. A significant decline in diversity of the benthic invertebrate community of the Tai Lake could be associated with continuous exposure to ammonia over decades given different sensitivity of taxa to ammonia. The results laid a scientific foundation for risk assessment and management of ammonia in Tai Lake, China, and the developed two-level risk assessment approach can also be applied to other similar aquatic regions.

Derivation of predicted no-effect concentration and ecological risk for atrazine better based on reproductive fitness.

Atrazine (ATZ) is an herbicide most commonly used in China and other regions of the world. It is reported toxic to aquatic organisms, and frequently occurs at relatively high concentrations. Currently, ATZ has been proved to affect reproduction of aquatic species at much lower levels. So it is controversial to perform ecological risk assessment using predicted no-effect concentrations (PENCs) derived from traditional endpoints, which fail to provide adequate protection to aquatic organisms. In this study, PNECs of ATZ were derived based on six endpoints of survival, growth, behavior, biochemistry, genetics and reproduction. The PNEC derived from reproductive lesion was 0.044µg ATZ L-1, which was obviously lower than that derived from other endpoints. In addition, a tiered ecological risk assessment was conducted in the Taizi River based on six PNECs derived from six categories of toxicity endpoints. Results of these two methods of ecological risk assessment were consistent with each other, and the risk level of ATZ to aquatic organisms reached highest as taking reproductive fitness into account. The joint probability indicated that severe ecological risk rooting in reproduction might exist 93.9% and 99.9% of surface water in the Taizi River, while 5% threshold (HC5) and 1% threshold (HC1) were set up to protect aquatic organisms, respectively. We hope the present work could provide valuable information to manage and control ATZ pollution.

ATXN7 Gene Variants and Expression Predict Post-Operative Clinical Outcomes in Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a lethal disease with nearly equal morbidity and mortality. Thus, the discovery and application of more useful predictive biomarkers for improving therapeutic effects and prediction of clinical outcomes is of crucial significance. METHODS: A total of 475 HBV-related HCC patients were enrolled. Ataxin 7 (ATXN7) single nucleotide polymorphisms (SNPs) were genotyped by Sanger DNA sequencing after PCR amplification. The associations between ATXN7 SNPs and mRNA expression with the prognosis of HBV-related HCC were analyzed. RESULTS: In all, rs3774729 was significantly associated with overall survival (OS) of HBV-related HCC (P = 0.013, HR = 0.66, 95% CI: 0.48-0.94). And patients with the AA genotype and a high level of serum alpha fetoprotein (AFP) had significantly worse OS when compared to patients with AG/GG genotypes and a low level of AFP (adjusted P = 0.007, adjusted HR = 1.83, 95% CI = 1.18-2.82). Furthermore, low expression of ATXN7 was significantly associated with poor recurrence-free survival (RFS) and OS (P = 0.007, HR = 2.38, 95% CI = 1.27-4.45 and P = 0.025, HR = 1.75, 95% CI = 1.18-2.62). CONCLUSION: ATXN7 may be a potential predictor of post-operative prognosis of HBV-related HCC.