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Transition metal nitrides have great potential applications as incompressible and high energy density materials. Various polymeric nitrogen structures significantly affect their properties, contributing to their complex bonding modes and coordination conditions. Herein, we first report a new manganese polynitride MnN 4 with bifacial trans-cis [N 4 ] n chains by treating with high-pressure and high-temperature conditions in a diamond anvil cell. Our experiments reveal that MnN 4 has a P -1 symmetry and could stabilize in the pressure range of 56-127 GPa. Detailed pressure-volume data and calculations of this phase indicate that MnN 4 is a potential hard (255 GPa) and high energy density (2.97 kJ/g) material. The asymmetric interactions impel N 1 and N 4 atoms to hybridize to sp 2-3 , which causes distortions of [N 4 ] n chains. This work discovers a new polynitride material, fills the gap for the study of manganese polynitride under high pressure, and offers some new insights into the formation of polymeric nitrogen structures.

With the development of industry and economy, ammonia nitrogen pollutions in surface water are of great concern worldwide. This study investigated the historical contents of total ammonia nitrogen (TAN) and unionized ammonia molecules (NH 3 ) in nine fresh lakes in China during 2014-2022. Three different classification methods (flood season, season, and geographical distribution) were used to analyze the concentration variation of TAN and NH 3 . The concentration of TAN first decreased and then increased in the flood season, showing a lower concentration in summer and a higher concentration in winter. The variation trend of NH 3 was in an opposite way with TAN. Correlation analysis between ammonia and 10 water quality parameters and 4 pollution emission and treatment parameters showed that the correlation coefficient between TAN and total phosphorus (total nitrogen) was 0.44 (0.43), respectively. The correlation coefficients between average annual TAN concentration and total emissions (waste water treatment input) were 0.35 (0.53), respectively. Combined with ecotoxicity data from a series of aquatic species, the ecological risks of TAN and NH 3 in lakes were evaluated using hazard quotient and joint probability curve methods. From 2014 to 2022, the probability of 5% species affected in the acute ecological risk of TAN and NH 3 is lower than 0.01, but for the chronic ecological risk of TAN and NH 3 , the probabilities of 5% species affected are 0.003-0.030 and 0.04-0.14, respectively. The chronic ecological risks were higher than the acute ecological risks, and high risks in plateau lakes like Dianchi Lake should be paid more attention to., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Research on liver aging has become prominent and has attracted considerable interest in uncovering the mechanism and therapeutic targets of aging to expand lifespan. In addition, multi-omics studies are widely used to perform further mechanistic investigations on liver aging. In this review, we illustrate the changes that occur with aging in the liver, present the current models of liver aging, and emphasize existing multi-omics studies on liver aging. We integrated the multi-omics data of enrolled studies and reanalyzed them to identify key pathways and targets of liver aging. The results indicated that C-X-C motif chemokine ligand 9 (Cxcl9) was a regulator of liver aging. In addition, we provide a flowchart for liver aging research using multi-omics analysis and molecular experiments to help researchers conduct further research. Finally, we present emerging therapeutic treatments that prolong lifespan. In summary, using cells and animal models of liver aging, we can apply a multi-omics approach to find key metabolic pathways and target genes to mitigate the adverse effects of liver aging., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aging is a contributor to liver disease. Hence, the concept of liver aging has become prominent and has attracted considerable interest, but its underlying mechanism remains poorly understood. In our study, the internal mechanism of liver aging was explored via multi-omics analysis and molecular experiments to support future targeted therapy. An aged rat liver model was established with d-galactose, and two other senescent hepatocyte models were established by treating HepG2 cells with d-galactose and H 2 O 2 . We then performed transcriptomic and metabolomic assays of the aged liver model and transcriptome analyses of the senescent hepatocyte models. In livers, genes related to peroxisomes, fatty acid elongation, and fatty acid degradation exhibited down-regulated expression with aging, and the hepatokine Fgf21 expression was positively correlated with the down-regulation of these genes. In senescent hepatocytes, similar to the results found in aged livers, FGF21 expression was also decreased. Moreover, the expressions of cell cycle-related genes were significantly down-regulated, and the down-regulated gene E2F8 was the key cell cycle-regulating transcription factor. We then validated that FGF21 overexpression can protect against liver aging and that FGF21 can attenuate the declines in the antioxidant and regenerative capacities in the aging liver. We successfully validated the results from cellular and animal experiments using human liver and blood samples. Our study indicated that FGF21 is an important target for inhibiting liver aging and suggested that pharmacological prevention of the reduction in FGF21 expression due to aging may be used to treat liver aging-related diseases., (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

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 one‑carbon 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., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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 Ca 2+ -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.

In order to avoid the high cost of existing precious metal catalyst like Pt, Ag/CeO 2 was the most promising catalysts for mobile source soot emission control technologies, but there was a clear trade-off between hydrothermal aging resistance and catalytic oxidation performance hindered the application of this catalyst. In order to reveal the hydrothermal aging mechanism of Ag/CeO 2 catalysts, the TGA (thermogravimetric analysis) experiments were investigated to reveal the mechanism of Ag modification on catalytic activity of CeO 2 catalyst between fresh and hydrothermal aging and were also characterized with the related characterization experiments to in-depth research the lattice morphology and valence changes. The degradation mechanism of Ag/CeO 2 catalysts in vapor with high-temperature was also explained and demonstrated based on density functional and molecular thermodynamics theories. The experimental and simulation data showed that the catalytic activity of soot combustion within Ag/CeO 2 decreased more significantly after hydrothermal aging than CeO 2 due to the less agglomerated, which caused by the decreased in O II /O I and Ce 3+ /Ce 4+ compared with CeO 2 . As shown in density function theory (DFT) calculation, the decreased surface energy and the increased oxygen vacancy formation energy of the low Mille index surface after Ag modification led to the instability structure and the high catalytic activity. Ag modification also increased the adsorption energy and Gibbs free energy of H 2 O on the low Miller index surface compared to CeO 2 , indicating that the desorption temperature of H 2 O molecules in (1 1 0) and (1 0 0) was higher than (1 1 1) in CeO 2 and Ag/CeO 2 , which led to the migration of (1 1 1) crystal surfaces to (1 1 0) and (1 0 0) in the vapor environment. These conclusions can provide a valuable addition to the regenerative application of Ce-based catalysts in diesel exhaust aftertreatment system the aerial pollution., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Aim: To investigate the interactions between the graft-to-recipient weight ratio (GWRWR) and other risk factors responsible for inferior allograft outcomes., Methods: A total of 362 patients who received liver transplantation (LT) were enrolled. Indicators such as graft/recipient weight and other prognostic factors were collected. Comparisons of indicators and survival analysis were performed in groups categorized by the GWRWR. Interactions of large-for-size grafts (LFSGs) with graft macrosteatosis (MaS) were evaluated in terms of relative excess risk caused by interaction (RERI) and attributable proportion (AP). Cytoscape visualized the role of LFSGs in the risk profile for poor prognosis., Results: Based on the GWRWR, LT cases can be categorized into three subgroups, standard (1%-2.5%), optimal (2.5%-3.0%), and inferior prognosis (>3.0%). Survival analysis confirmed clear separations in cases categorized by the above-defined limits on the GWRWR ( P  < 0.05). LFSGs caused inferior prognosis by initiating positive interactions with MaS severity., Conclusion: The GWRWR exerted nonlinear effects on prognosis in deceased donor LT cases. LFSGs (GWRWR > 3.0%) caused inferior outcomes, while grafts sized within (2.5%-3.0%) had optimal post-transplant prognosis. MaS increased the risk of poor prognosis by exerting positive synergistic effects on LFSGs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Liu, Lyu, Li, Yu, Que, Xu, Geng and Zheng.)

Ecological risks can vary dramatically depending on abiotic factors, such as soil properties and the background values of elements. This study developed a framework for an integrated risk assessment system to derive soil quality criteria (SQC) for heavy metals (HMs) applicable to different soil types and to assess ecological risks at a multi-regional scale. Through the construction of normalization and species sensitivity distribution models, 248 SQC values for Cd, Pb, Zn, As, Cu, Cr, Sb, and Ni in 31 Chinese provinces were derived. These SQC considered the soil types and background values of the elements and effectively reduced the uncertainty caused by spatial heterogeneity. Using the derived SQC values, the qualitative and quantitative ecological risks of HMs in the terrestrial environment of China were comprehensively assessed using a three-level ecological risk assessment (ERA) approach. Compared to traditional ERA methods, the new methodology reached a more quantitative conclusion. The mean overall probabilities of ecological risk in China were 2.42 % (Cd), 2.82 % (Pb), 12.17 % (Zn), 14.89 % (As), 10.42 % (Cu), 32.20 %(Cr), and 8.88 % (Ni). The new framework could be useful for the ERA of various soil types., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In vitro assembly of amyloid fibrils that recapitulate those in human brains is very useful for fundamental and applied research on the amyloid formation, pathology, and clinical detection. Recent success in the assembly of Tau fibrils in vitro enables the recapitulation of the paired helical filament (PHF) of Tau extracted from brains of patients with Alzheimer's disease (AD). However, following the protocol, we observed that Tau constructs including 297-391 and a mixture of 266-391 (3R)/297-391, which are expected to predominantly form PHF-like fibrils, form highly heterogeneous fibrils instead. Moreover, the seemingly PHF-like fibril formed by Tau 297-391 exhibits a distinctive atomic structure with a spindle-like fold, that is neither PHF-like or similar to any known Tau fibril structures revealed by cryo-electron microscopy (cryo-EM). Our work highlights the high sensitivity of amyloid fibril formation to subtle conditional changes and suggests high-resolution structural characterization to in vitro assembled fibrils prior to further laboratory use., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

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 KH 20 and KH 30 , hosting high superconducting transition temperatures ( T c ) 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- T c . 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 H 36 cages. These results offer key insights into the stability and potential high- T c superconductivity of compressed extreme superhydrides and will further stimulate related research.

Omics data address key issues in liver transplantation (LT) as the most effective therapeutic means for end-stage liver disease. The purpose of this study was to review the current application and future direction for omics in LT. We reviewed the use of multiomics to elucidate the pathogenesis leading to LT and prognostication. Future directions with respect to the use of omics in LT are also described based on perspectives of surgeons with experience in omics. Significant molecules were identified and summarized based on omics, with a focus on post-transplant liver fibrosis, early allograft dysfunction, tumor recurrence, and graft failure. We emphasized the importance omics for clinicians who perform LTs and prioritized the directions that should be established. We also outlined the ideal workflow for omics in LT. In step with advances in technology, the quality of omics data can be guaranteed using an improved algorithm at a lower price. Concerns should be addressed on the translational value of omics for better therapeutic effects in patients undergoing LT., Competing Interests: The authors have no conflict of interests related to this publication., (© 2022 Authors.)

Lanthanum (La), the first member of the lanthanide elements, recently aroused interests due to the discovery of high- T c superconductor LaH 10 under high pressures and its unique superconducting properties. Here, we study the phase transitions, superconductivity and mechanical properties of metallic La under high pressures by first-principle calculations. The known face-centered cubic (fcc) phase with space groupFm3¯mstill exists above 100 GPa. And it transforms into an unprecedented body-centered tetragonal (bct) phase with space group I 4/ mmm above 180 GPa, which expands the high pressure phase transition sequence. Further calculations show that the superconducting transition temperature T c of fcc phase decreases with increasing pressure with the rate of -0.13 K GPa -1 , in good agreement with the experimental results. For the bct phase, the estimated superconducting transition temperature is very low with T c of 0.7 K at 200 GPa. The calculations of mechanical properties show that both of fcc and bct phases are compressible and brittle., (© 2022 IOP Publishing Ltd.)

Background: Low-grade glioma (LGG) is considered a fatal disease for young adults, with overall survival widely ranging from 1 to 15 years depending on histopathologic and molecular subtypes. As a novel type of programmed cell death, ferroptosis was reported to be involved in tumorigenesis and development, which has been intensively studied in recent years. Methods: For the discovery cohort, data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were used to identify the differentially expressed and prognostic ferroptosis-related genes (FRGs). The least absolute shrinkage and selection operator (LASSO) and multivariate Cox were used to establish a prognostic signature with the above-selected FRGs. Then, the signature was developed and validated in TCGA and Chinese Glioma Genome Atlas (CGGA) databases. By combining clinicopathological features and the FRG signature, a nomogram was established to predict individuals' one-, three-, and five-year survival probability, and its predictive performance was evaluated by Harrell's concordance index (C-index) and calibration curves. Enrichment analysis was performed to explore the signaling pathways regulated by the signature. Results: A novel risk signature contains seven FRGs that were constructed and were used to divide patients into two groups. Kaplan-Meier (K-M) survival curve and receiver-operating characteristic (ROC) curve analyses confirmed the prognostic performance of the risk model, followed by external validation based on data from the CGGA. The nomogram based on the risk signature and clinical traits was validated to perform well for predicting the survival rate of LGG. Finally, functional analysis revealed that the immune statuses were different between the two risk groups, which might help explain the underlying mechanisms of ferroptosis in LGG. Conclusion: In conclusion, this study constructed a novel and robust seven-FRG signature and established a prognostic nomogram for LGG survival prediction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Liu, Zheng, Gao and Li.)

Background: Pyruvate kinase L/R (PKLR) has been suggested to affect the proliferation of hepatocytes via regulation of the cell cycle and lipid metabolism. However, its impact on the global metabolome and its clinical implications remain unclear., Aims: We aimed to clarify the genetic impact of PKLR on the metabolomic profiles of hepatoma cells and its potential effects on grafts for liver transplantation (LT)., Methods: Nontargeted and targeted metabolomic assays were performed in human hepatoma cells transfected with lentiviral vectors causing PKLR overexpression and silencing, respectively. We then constructed a molecular network based on integrative analysis of transcriptomic and metabolomic data. We also assessed the biological functions of PKLR in the global metabolome in LT grafts in patients via a weighted correlation network model., Results: Multiomic analysis revealed that PKLR perturbations significantly affected the pyruvate, citrate, and glycerophospholipid metabolism pathways, as crucial steps in de novo lipogenesis (DNL). We also confirmed the importance of phosphatidylcholines (PC) and its derivative lyso-PC supply on improved survival of LT grafts in patients. Coexpression analysis revealed beneficial effects of PKLR overexpression on posttransplant prognosis by alleviating arachidonic acid metabolism of the grafts, independent of operational risk factors., Conclusion: This systems-level analysis indicated that PKLR affected hepatoma cell viability via impacts on the whole process of DNL, from glycolysis to final PC synthesis. PKLR also improved prognosis after LT, possibly via its impact on the increased genesis of beneficial glycerophospholipids., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Zhengtao Liu et al.)

All elements that form diatomic molecules, such as H&#95;{2}, N&#95;{2}, O&#95;{2}, Cl&#95;{2}, Br&#95;{2}, and I&#95;{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&#95;{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.

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., Competing Interests: The authors declare no competing interest.

Background: Donor age affects allograft quality and the prognosis of recipients after liver transplantation (LT). Clinicians have assessed the quality of grafts from older donors based on their appearance and texture, with no reliable quantitative evidence. Our study aimed to assess the quantitative impact of donor age on post-transplant outcomes and its safety threshold for LT, based on the published literature. Methods: Relevant studies were retrieved from the Embase, PubMed, and ISI Web of Science databases. Pooled dichotomous relative risks (RRs) were calculated using metan. Continuous RRs were calculated using a two-stage random-effects model. Results: Eleven studies including 30,691 LT cases were included for further analysis. For categorical comparison, the RR of death within the first post-transplant year was significantly higher among patients who received grafts from older donors. Similarly, the RR of graft failure (GF) was increased within the 3 years after transplantation. For continuous comparison, advanced donor age affected transplant outcomes in a linear manner ( P > 0.05). A 10-year increment in donor age was associated with RRs 1.10, 1.12, 1.15, 1.10, and 1.08 for 90-day, 180-day, 1-year, 3-year, and 5-year patient mortality and 1.08, 1.06, 1.10, 1.11, and 1.12, for 90-day, 180-day, 1-year, 2-year, and 3-year GF, respectively (all P < 0.05). A spline model showed that transplants using grafts from donors <43 years old were not associated with age-related risks ( P > 0.05). The risk of GF was increased in subgroups with fewer LT cases, longer cold ischemic time, fewer male donors, and recipients with viral hepatitis ( P < 0.05). Conclusion: Donor age might affect post-LT outcomes in a dose-dependent manner. The safety threshold for donor age in terms of GF should be lowered to 43 years as an early warning for the guarantee of satisfactory outcomes. Clinicians should weigh the benefits against the risks carefully for patients receiving grafts from older donors. Further studies are warranted to investigate the mechanisms responsible for the relationship between donor age and graft quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Liu, Qian, Xu, Que, Zhuang, Geng, Zhou and Zheng.)

Background: Liver transplantation (LT) is one of the most effective surgical treatment for patients with end-stage liver disease. Steatosis is a contributor for inferior graft quality. But its impact and safety on transplantation was less assessed in Chinese patients., Methods: Graft steatosis and related information involved in recipients, donors and surgical procedures were retrospectively collected from 239 patients., Results: Donor macrosteatosis (MaS) caused about 2.14 and 2.80 folds of increment on patient and graft mortality. Dose-response analysis revealed prominent risk of grafts on overall patient/organ mortality when MaS content exceeded 10% (P<0.05). Noteworthy, deaths were only observed in MaS group when concurrent with extremely higher post-transplant alanine aminotransferase (ALT, 64%). However, microsteatosis (MiS) grafts didn't affect outcomes after LT. In a cohort of Chinese patients, MaS had comprehensive effects on post-transplant outcomes with relatively lower safety threshold at 10%. Mortality gap caused by MaS grafts was observed in patients with severer ischemia reperfusion injury., Conclusions: Our study revealled the graft MaS affected the post-transplant outcomes in lower risk cutoff in Chinese patients. Further study is worthy to validate these results and investigate inner mechanism under the phenomenon., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/hbsn.2019.12.02). The authors have no conflicts of interest to declare., (2020 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Background: Exposure to dietary aflatoxin B1 (AFB1) induces DNA damage and mutation in the TP53 gene at codon 249, known as the TP53 R249S mutation, and is a major risk factor for hepatocellular carcinoma (HCC). AFB1 and the hepatitis B virus (HBV) together exert synergistic effects that promote carcinogenesis and TP53 R249S mutation in HCC., Methods: A genome-wide association study (GWAS) of whole genome exons was conducted using 485 HCC patients with chronic HBV infection. This was followed by an independent replication study conducted using 270 patients with chronic HBV infection. Immunohistochemistry was used to evaluate TP53 expression in all samples. This showed a correlation between codon 249 mutations and TP53 expression. Susceptibility variants for the TP53 R249S mutation in HCC were identified based on both the GWAS and replication study. The associations between identified variants and the expression levels of their located genes were analyzed in 20 paired independent samples., Results: The likelihood of positive TP53 expression was found to be higher in HCC patients with the R249S mutation both in the GWAS (P<0.001) and the replication study (P=0.006). The combined analyses showed that the TP53 R249S mutation was significantly associated with three single nucleotide polymorphisms (SNPs): ADAMTS18 rs9930984 (adjusted P=4.84×10 -6 ), WDR49 rs75218075 (adjusted P=7.36×10 -5 ), and SLC8A3 rs8022091 (adjusted P=0.042). The TP53 R249S mutation was found to be highly associated with the TT genotypes of rs9930984 (additive model, P=0.01; dominant model, P=6.43×10 -5 ) and rs75218075 (additive model, P=0.002; dominant model, P=2.16×10 -4 ). Additionally, ADAMTS18 mRNA expression was significantly higher in HCC tissue compared with its expression in paired non-tumor tissue (P=0.041), and patients carrying the TT genotype at rs9930984 showed lower ADAMTS18 expression in non-tumor tissue compared with patients carrying the GT genotype (P=0.0028). WDR49 expression was markedly lower in HCC tissue compared with paired non-tumor tissue (P=0.0011)., Conclusions: TP53 expression is significantly associated with the R249S mutation in HCC. Our collective results suggest that rs9930984, rs75218075, and rs8022091 are associated with R249S mutation susceptibility in HCC patients exposed to AFB1 and HBV infection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-20-510). The authors have no conflicts of interest to declare., (2020 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: Our previous study revealled amplified hazardous effects of macrosteatosis (MaS) on graft failure (GF) in recipients with severe liver damage in short post-operative days, with vague mechanism inside., Aim: We aimed to uncover the molecular mechanism of donor MaS on GF, and construct the predictive model to monitor post-transplant prognosis based on "omics" perspective., Methods: Ultra-performance liquid chromatography coupled to mass spectrometry metabolomic analysis was performed in allograft tissues from 82 patients with initial poor function (IPF) from multi-liver transplant (LT) centers. Pathway analysis was performed by on-line toolkit Metaboanalyst (v 3.0). Predictive model was constructed based on combinative metabonomic and clinical data extracted by stepwised cox proportional analysis., Results: Principle component analysis (PCA) analysis revealled stratification on metabolic feature in organs classified by MaS status. Differential metabolits both associated with MaS and GF were significantly enriched on pathway of glycerophospholipid metabolism ( P < 0.05). Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) involved in glycerophospholipid metabolism was significantly decreased in cases with MaS donors and GF ( P < 0.05). Better prediction was observed on graft survival by combinative model (area under the curve = 0.91) and confirmed by internal validation., Conclusion: Metabonomic features of allografts can be clearly distinguished by MaS status in patients with IPF. Dysfunction on glycerophospholipid metabolism was culprit to link donor MaS and final GF. Decrement on PC and PE exerted the fatal effects of MaS on organ failure. Metabonomic data might help for monitoring long-term graft survival after LT., (Copyright © 2020 Liu, Zhu, Wang, Xu, Que, Zhuang, Qian, Wang, Yu, Zhang, Yin, Xie, Zhou, Geng and Zheng.)

Background: Hepatitis B virus (HBV) infection and dietary aflatoxin exposure are two major and synergistic carcinogenic factors of hepatocellular carcinoma (HCC) in southern China. Mutation of the TP53 gene at codon 249 (TP53 249Ser) is recognized as a fingerprint of aflatoxin B1 (AFB1) exposure., Methods: A total of 485 HCC patients positive for serum hepatitis B surface antigen were enrolled. The clinicopathological information and survival time were collected. TP53 249Ser mutations in HCC were detected by Sanger DNA sequencing after PCR amplification. Immunohistochemical staining was used to evaluate TP53 expression. Propensity score matching (PSM) and Cox proportional hazards regression (CPHR) were conducted to identify independent risk factors for prognosis that were incorporated into the nomogram. Univariate logistic regression analysis was used to compare differences in clinical factors between the TP53 249Ser mutation group and the non-mutation group. A Kaplan-Meier plot, univariate and multivariate Cox proportional hazards models were used to assess the association between clinicopathological characteristics and survival outcomes., Results: After PSM, a total of 322 cases were included in the analysis of clinical prognosis. Results of CPHR showed that the mutation group had a relatively higher risk of tumor recurrence within 2 years after undergoing hepatectomy (P=0.039, HR =1.47, 95% CI: 1.02-2.18). The prognostic model performed better in terms of 2-year DFS prediction than BCLC stage. Patients who had a nomogram score of more than 160 were considered to have a higher risk of recurrence within 2 years., Conclusions: Our study found that the TP53 249Ser mutation may be a high risk factor of HBV-related HCC recurrence in the short term. And we initially established a nomogram scoring system for predicting 2-year recurrence in HBV-related HCC patients in southern China., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-19-2788). The authors have no conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

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., (Copyright © 2019 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Epidemiological survey identified that the variant patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene at I148M position exerts direct effect in promoting hepatocellular carcinoma (HCC) under extraneous oxidative stress by interaction with obesity. However, the mechanism is still unknown. HepG2 cells were overexpressed by transinfection of PNPLA3 with wild-type 148I (PNPLA3(WT)) and mutant 148M (PNPLA3(I148M)), respectively. Variation in metabolic indicators, hepatic steatosis, biological behaviors and signaling molecules related to cancer promotion was measured in hepatocytes using low-dose free fatty acid (FFA) exposure. Effect of PNPLA3(I148M) on xenograft biology and its interaction with dietary obesity were also evaluated in animal study. Cells overexpresssing PNPLA3(I148M) in low-dose FFA incubation showed more proliferation, migration, invasion, and less apoptosis (P<0.05). Low-dose FFA specifically activated JAK2/STAT3 phosphorylation of PNPLA3(I148M) cells via upregulation of interleukin-6. Animal study showed high-fat diet accelerated growth of xenografts derived from PNPLA3(I148M) cells incubated in low-dose FFA. In low oxidative stress, PNPLA3(I148M) initiated the hepatocyte malignant transformation through the activation of inflammation-mediated JAK/STAT pathway. Dietary obesity amplified the growth of tumor from PNPLA3(I148M) cells by interaction with local FFA incubation. Anti-inflammation and weight loss might be potential approaches for preventing HCC in high-risk population carrying PNPLA3 variant.

China has recently commenced water quality criteria (WQC) research using the species sensitivity distribution (SSD) method; however, it is difficult to obtain sufficient native species toxicity data for thousands of contaminants. In this study, the feasibility of using non-native toxicity data in deriving native WQC was analyzed. We constructed SSDs based on acute toxicity data of species from China and the USA for eight priority pollutants, and compared the sensitivities of different taxonomic groups between the two countries. The results showed that the SSD method of log-logistic distribution fit the toxicity data of different taxa well. The comparison of sensitivity distribution and hazardous concentration for 5% of the species and 50% of the species showed that there was no significant difference between Chinese and American taxa. It could be feasible to use toxicity data from the USA to provide a temporary way to protect organisms in China in emergency situations or for management of priority pollutants when native toxicity data are lacking.

The aim of this study was to evaluate the toxicological responses of earthworm (Eisenia fetida) induced by field-contaminated, metal-polluted soils. Biochemical responses and DNA damage of earthworm exposed to two multi-metal-contaminated soils in a steel industry park and a natural reference soil in Zijin Mountain for 2, 7, 14, and 28 days were studied. Results showed that three enzyme activities, including superoxide dismutase (SOD), acetylcholinesterase (AChE), and cellulase, in earthworm in metal-contaminated soils were significantly different from those of the reference soil. Cellulase and AChE were more sensitive than SOD to soil contamination. The Olive tail moment of the comet assay after 2-day exposure increased 56.5 and 552.0 % in two contaminated soils, respectively, compared to the reference soil. Our findings show that cellulase and DNA damage levels can be used as potential biomarkers for exposure of earthworm to metal-polluted soils.

The acute and sub-chronic toxicities of cyanobacterial extract from Taihu Lake (PR China) on mouse (Mus musculus) were investigated in this study via intraperitoneal (i.p.) injection. Increases in liver/body weight ratios and pathological changes in mouse liver showed adverse effects at the organ level. Images from transmission electron microscopy (TEM) indicated that abnormal membrane structure occurred and that the organelles were damaged severely in the cells of liver and testis. The high dose group received i.p. injection of 12 mg lyophilized algae cells/kg body weight. Malondialdehyde (MDA) levels increased significantly in the livers of this group, along with a significant decrease in catalase (CAT) activity. These results revealed the existence of obvious oxidative stress. Comet assay results also suggested a dose-dependent relationship between DNA damage in hepatocytes/testicular cells and the amount of bloom extract administered to the mice. There was a significant increase in DNA damage compared to the control group and the genotoxicity of the cyanobacterial bloom to testicular cells was higher than in hepatocytes.

Twenty one surface sediments were analyzed for PCDD/Fs and dioxin-like PCBs by HRGC-HRMS in Yellow Estuary and Yangtze Estuary in China. The concentration ranges of 2,3,7,8-substituted PCDD/Fs, dioxin-like PCBs and WHO-TEQ were 2.33-253, 0.04-139 and 0.11-1.01 pg/g dw respectively in sediment from two estuaries. For PCDD/Fs and dioxin-like PCBs, OCDD, CB77, CB105 and CB118 were found to be dominant. The pollution levels in two estuaries were lower compared with that in other locations reported by previous studies.