DNA methylation regulator-based molecular subtyping and tumor microenvironment characterization in hepatocellular carcinoma.

Backgroud: Although recent studies have reported the regulation of the immune response in hepatocellular carcinoma (HCC) through DNA methylation, the comprehensive impact methylation modifications on tumor microenvironment characteristics and immunotherapy efficacy has not been fully elucidated. Methods: In this research, we conducted a comprehensive assessment of the patterns of DNA methylation regulators and the profiles of the tumor microenvironment (TME) in HCC, focusing on 21 specific DNA methylation regulators. We subsequently developed a unique scoring system, a DNA methylation score (DMscore), to assess the individual DNA methylation modifications among the three distinct methylation patterns for differentially expressed genes (DEGs). Results: Three distinct methylation modification patterns were identified with distinct TME infiltration characteristics. We demonstrated that the DMscore could predict patient subtype, TME infiltration, and patient prognosis. A low DMscore, characterized by an elevated tumor mutation burden (TMB), hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, and immune activation, indicates an inflamed tumor microenvironment phenotype with a 5-year survival rate of 7.8%. Moreover, a low DMscore appeared to increase the efficacy of immunotherapy in the anti-CTLA-4/PD-1/PD-L1 cohort. Conclusions: In brief, this research has enhanced our understanding of the correlation between modifications in DNA methylation patterns and the profile of the tumor microenvironment in individuals diagnosed with HCC. The DMscore may serve as an alternative biomarker for survival and efficacy of immunotherapy in patients with HCC.

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.

Integrated lipidomic and transcriptomic analyses reveal the mechanism of lipid biosynthesis and accumulation during seed development in sesame.

Sesame is one of the most important oilseed crops and attracts significant attention because of its huge nutritional capacity. However, the molecular mechanisms underlying oil accumulation in sesame remains poorly understood. In this study, lipidomic and transcriptomic analyses in different stages of sesame seed (Luzhi No.1, seed oil content 56%) development were performed to gain insight into the regulatory mechanisms that govern differences in lipid composition, content, biosynthesis, and transport. In total, 481 lipids, including fatty acids (FAs, 38 species), triacylglycerol (TAG, 127 species), ceramide (33 species), phosphatidic acid (20 species), and diacylglycerol (17 species), were detected in developing sesame seed using gas and liquid chromatography-mass spectrometry. Most FAs and other lipids accumulated 21-33 days after flowering. RNA-sequence profiling in developing seed highlighted the enhanced expression of genes involved in the biosynthesis and transport of FAs, TAGs, and membrane lipids, which was similar to that seen during lipid accumulation. Through the differential expression analysis of genes involved in lipid biosynthesis and metabolism during seed development, several candidate genes were found to affect the oil content and FA composition of sesame seed, including ACCase, FAD2, DGAT, G3PDH, PEPCase, WRI1 and WRI1-like genes. Our study reveals the patterns of lipid accumulation and biosynthesis-related gene expression and lays an important foundation for the further exploration of sesame seed lipid biosynthesis and accumulation.

A glutathione S-transferase GhTT19 determines flower petal pigmentation via regulating anthocyanin accumulation in cotton.

Anthocyanin accumulations in the flowers can improve seed production of hybrid lines, and produce higher commodity value in cotton fibre. However, the genetic mechanism underlying the anthocyanin pigmentation in cotton petals is poorly understood. Here, we showed that the red petal phenotype was introgressed from Gossypium bickii through recombination with the segment containing the R3 bic region in the A07 chromosome of Gossypium hirsutum variety LR compared with the near-isogenic line of LW with white flower petals. The cyanidin-3-O-glucoside (Cy3G) was the major anthocyanin in red petals of cotton. A GhTT19 encoding a TT19-like GST was mapped to the R3 bic site associated with red petals via map-based cloning, but GhTT19 homologue gene from the D genome was not expressed in G. hirsutum. Intriguingly, allelic variations in the promoters between GhTT19LW and GhTT19LR , rather than genic regions, were found as genetic causal of petal colour variations. GhTT19-GFP was found localized in both the endoplasmic reticulum and tonoplast for facilitating anthocyanin transport. An additional MYB binding element found only in the promoter of GhTT19LR , but not in that of GhTT19LW , enhanced its transactivation by the MYB activator GhPAP1. The transgenic analysis confirmed the function of GhTT19 in regulating the red flower phenotype in cotton. The essential light signalling component GhHY5 bonded to and activated the promoter of GhPAP1, and the GhHY5-GhPAP1 module together regulated GhTT19 expression to mediate the light-activation of petal anthocyanin pigmentation in cotton. This study provides new insights into the molecular mechanisms for anthocyanin accumulation and may lay a foundation for faster genetic improvement of cotton.

Effect of Different Mo Addition on Microstructure and Mechanical Properties of Cu-15Ni-8Sn Alloy.

In the present study, Mo was added to Cu-15Ni-8Sn alloy as the fourth element to solve the limitation of service performance of the alloy by composition design. The phase composition, microstructure transformation and mechanical properties of Cu-15Ni-8Sn-xMo (x = 0.3, 0.9, 1.5 wt.%) alloy were systematically studied by simulation calculation and experimental characterization. The results show that the addition of Mo can improve the as-cast structure of Cu-15Ni-8Sn alloy and reduce segregation and Cu-Mo phase precipitates on the surface with the increase in Mo contents. During solution treatment, Mo can partially dissolve into the matrix, which may be the key to improving the properties of the alloy. Furthermore, the discontinuous precipitation of Sn can be effectively inhibited by adding the appropriate amount of Mo to Cu-15Ni-8Sn alloy, and the hardness of alloy does not decrease greatly after a long-time aging treatment. When Mo content is 0.9 wt.%, the alloy reaches the peak hardness of 384 HV at 4 h of aging. These results provide new ideas for composition optimization of Cu-15Ni-8Sn alloy.

The Microstructural Evolution of Cu-Sn-P Alloy during Hot Deformation Process.

The microstructure evolution of Cu-Sn-P alloy subjected to hot deformation was researched through electron backscatter diffraction (EBSD) and transmission electron microscope (TEM) in the present study. The results indicated that after hot deformation, grains perpendicular to the force direction were elongated, and mostly became deformed grains, and then exhibited an obvious hardening effect. The Cu-Sn-P alloy could be strain hardened during hot deformation, but, with recrystallization, a softening effect occurred. Changes in dislocation density, textures, and grain sizes play different roles in flow stress behaviors of Cu-Sn-P alloy, and the dislocation density has a more evident effect at low temperature. However, with increase in temperature, recrystallization softening gradually dominates. Low-angle grain boundaries (LABs) account for the majority of hot deformed microstructures of Cu-Sn-P alloy. High dislocation densities in these zones make it easy to initiate the dislocation slipping systems. Deformation is realized through dislocation slipping and the slipping of edge dislocation pairs. The dislocation pile-up zones have high distortion energies, and, thus, elements of diffusion and recrystallization nucleation can occur easily. At different temperatures, the maximum polar density of textures gradually increases, and there are preferred orientations of grains. At 500 °C, stacking faults accumulate and promote the growth of twins. The twin growth direction is mainly determined by the migration of high-angle grain boundaries (HABs) and the clustering of high-stress zones.

Metabolomics and Transcriptomics Analysis of Pollen Germination Response to Low-Temperature in Pitaya (Hylocereus polyrhizus).

Cross-pollination can improve the percentage of fruit set and fruit weight for most red flesh varieties in pitaya. The technology of pollen storage was very important for successful cross-pollination. However, till present, the technology of pollen storage is unsatisfactory in pitaya production. In this study, pitaya pollen stored at low temperature was taken as the research object, and its physicochemical indexes, metabolomics, and transcriptomics were studied. The results showed that in vitro pollen germination rate decreased significantly with the increase in storage time. Soluble sugar and soluble protein content of pollen peaked on the first day of storage, whereas its relative conductivity, and manlondialdehyde (MDA) and proline contents increased gradually during storage. At the same time, the antioxidant enzyme system of pollen was also affected. Superoxide dismutase (SOD) activity decreased, while the activities of catalase (CAT) and peroxidase (POD) increased and superoxide anion generation rate increased gradually during storage. According to the metabolomics results, amino acid, peptide, nucleotide, plant hormone, terpene, alcohol, phenol, flavonoid, sterol, vitamin, ester, sphingolipid, and ketone contents increased significantly during storage, whereas flavonoid and pigment contents declined gradually. During pollen storage, the gene expressions related to carbohydrate metabolism, protein metabolism, acid and lipid metabolism, sterol metabolism, plant hormone metabolism, and signal transductions were significantly downregulated. With KEGG pathway analysis, isoquinoline alkaloid biosynthesis, tyrosine metabolism, alanine, aspartate, and glutamate metabolism of pollen were affected significantly during low-temperature storage. Correlation analysis showed that the gene expression patterns of HuRP2, HuUPL1, and HuAAT2 had significant effects on pollen germination. D-arabinose 5-phosphate and myricetin were positively correlated with pollen germination rate, which was valuable for studying preservation agents. In this study, the changes in pollen during low-temperature storage were described from the level of metabolites and genes, which could provide theoretical support for the research and development of pollen long-term storage technology in pitaya.

Integrating the Epigenome and Transcriptome of Hepatocellular Carcinoma to Identify Systematic Enhancer Aberrations and Establish an Aberrant Enhancer-Related Prognostic Signature.

Recently, emerging evidence has indicated that aberrant enhancers, especially super-enhancers, play pivotal roles in the transcriptional reprogramming of multiple cancers, including hepatocellular carcinoma (HCC). In this study, we performed integrative analyses of ChIP-seq, RNA-seq, and whole-genome bisulfite sequencing (WGBS) data to identify intergenic differentially expressed enhancers (DEEs) and genic differentially methylated enhancers (DMEs), along with their associated differentially expressed genes (DEE/DME-DEGs), both of which were also identified in independent cohorts and further confirmed by HiC data. Functional enrichment and prognostic model construction were conducted to explore the functions and clinical significance of the identified enhancer aberrations. We identified a total of 2,051 aberrant enhancer-associated DEGs (AE-DEGs), which were highly concurrent in multiple HCC datasets. The enrichment results indicated the significant overrepresentations of crucial biological processes and pathways implicated in cancer among these AE-DEGs. A six AE-DEG-based prognostic signature, whose ability to predict the overall survival of HCC was superior to that of both clinical phenotypes and previously published similar prognostic signatures, was established and validated in TCGA-LIHC and ICGC-LIRI cohorts, respectively. In summary, our integrative analysis depicted a landscape of aberrant enhancers and associated transcriptional dysregulation in HCC and established an aberrant enhancer-derived prognostic signature with excellent predictive accuracy, which might be beneficial for the future development of epigenetic therapy for HCC.

Molecular Dynamics Study on Mechanical Properties of Nanopolycrystalline Cu-Sn Alloy.

Molecular dynamics simulation is one kinds of important methods to research the nanocrystalline materials which is difficult to be studied through experimental characterization. In order to study the effects of Sn content and strain rate on the mechanical properties of nanopolycrystalline Cu-Sn alloy, the tensile simulation of nanopolycrystalline Cu-Sn alloy was carried out by molecular dynamics in the present study. The results demonstrate that the addition of Sn reduces the ductility of Cu-Sn alloy. However, the elastic modulus and tensile strength of Cu-Sn alloy are improved with increasing the Sn content initially, but they will be reduced when the Sn content exceeds 4% and 8%, respectively. Then, strain rate ranges from 1 × 109 s-1 to 5 × 109 s-1 were applied to the Cu-7Sn alloy, the results show that the strain rate influence elastic modulus of nanopolycrystalline Cu-7Sn alloy weakly, but the tensile strength and ductility enhance obviously with increasing the strain rate. Finally, the microstructure evolution of nanopolycrystalline Cu-Sn alloy during the whole tensile process was studied. It is found that the dislocation density in the Cu-Sn alloy reduces with increasing the Sn content. However, high strain rate leads to stacking faults more easily to generate and high dislocation density in the Cu-7Sn alloy.

Prognostic Model and Nomogram Construction Based on a Novel Ferroptosis-Related Gene Signature in Lower-Grade Glioma.

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.

Topological Alterations of Working Memory Impairment in Aged Patients With Vascular Dementia.

Aneurysmal subarachnoid hemorrhage (aSAH) is a common disease causing vascular dementia. Survivors often suffer from cognitive impairment especially working memory deficit. Currently, lack of theoretical support limits the improvement of cognitive intervention or rehabilitation. It is unclear how the large-scale network differs and to what extent is the brain network affected? Our study aims to provide novel information about the topological characteristics of brain organization, especially "small-world" property. A total of 62 aSAH patients are enrolled in this study. They are divided into two groups according to the syndrome of working memory deficit. Their working memory function is evaluated by TMT-B and AVLT (Chinese version). Functional MRI scan is also performed for detecting resting-state cortical plasticity. We utilized ICA to extract functional sub-networks including working memory network from imaging data. And then we establish binarized network and calculate the small-worldness property as well as local and global efficiency of networks. aSAH group with working memory deficit shows no significant difference of clustering coefficient with control group. Our study discovered significant decrease of characteristic path length indicating an increase of overall routing efficiency. We reason that patients with working memory deficit have to recruit more neuronal resources and thus develops higher overall routing efficiency of local network. This study provides novel information about the neural alterations of aSAH patients with working memory deficit. It might contribute to the understanding of neural mechanism and the improvement of current intervention for vascular dementia.

Integrative Network Analysis Revealed Genetic Impact of Pyruvate Kinase L/R on Hepatocyte Proliferation and Graft Survival after Liver Transplantation.

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.

Revealing the Effect of Phase Composition and Transformation on the Mechanical Properties of a Cu-6Ni-6Sn-0.6Si Alloy.

In the present study, a Cu-6Ni-6Sn-0.6Si alloy is fabricated through frequency induction melting, then subjected to solution treatment, rolling, and annealing. The phase composition, microstructure evolution, and transition mechanism of the Cu-6Ni-6Sn-0.6Si alloy are researched systematically through simulation calculation and experimental characterization. The ultimate as-annealed sample simultaneously performs with high strength and good ductility according to the uniaxial tensile test results at room temperature. There are amounts of precipitates generated, which are identified as belonging to the DO22 and L12 phases through the transmission electron microscope (TEM) analysis. The DO22 and L12 phase precipitates have a significant strengthening effect. Meanwhile, the generation of the common discontinuous precipitation of the γ phase, which is harmful to the mechanical properties of the copper-nickel-tin alloy, is inhibited mightily during the annealing process, possibly due to the existence of the Ni5Si2 primary phase. Therefore, the as-annealed sample of the Cu-6Ni-6Sn-0.6Si alloy possesses high tensile strength and elongation, which are 967 MPa and 12%, respectively.

Correlation Between Prognostic Biomarker SLC1A5 and Immune Infiltrates in Various Types of Cancers Including Hepatocellular Carcinoma.

BACKGROUND: Solute carrier family 1 member 5 (SLC1A5) is a major glutamine transporter and plays a key role in tumor growth. The main objectives of this study were to visualize the prognostic landscape of SLC1A5 in multiple cancers and determine the relations between SLC1A5 expression and tumor immunity. METHODS: SLC1A5 expression and its effect on tumor prognosis were analyzed using multiple online tools Oncomine, Gene Expression Profiling Interactive Analysis, PrognoScan, and Kaplan-Meier plotter with their own datasets as well as the data from The Cancer Genome Atlas. The correlations between SLC1A5 and tumor immune infiltrates were determined via TIMER. RESULTS: SLC1A5 expression was significantly higher in several types of cancers, including hepatocellular carcinoma (HCC), compared with corresponding normal tissues. High SLC1A5 expression correlated with poor overall survival and with disease-free survival related to alcohol consumption. Moreover, SLC1A5 expression correlated positively with the numbers of tumor-infiltrating B cells, CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells in HCC and in lower-grade glioma (LGG). Also, SLC1A5 expression showed strong correlations with diverse immune marker sets in HCC and LGG, indicating its role in regulating tumor immunity. CONCLUSIONS: SLC1A5 represents a useful prognostic biomarker in multiple cancers, and its expression correlates highly with tumor immune-cell infiltration, especially in HCC and LGG.

Analysis of the misdiagnosis of 8 adult cases of paragonimiasis with lung masses as the main manifestation in Xishuangbanna, Yunnan.

OBJECTIVE: To summarize the clinical characteristics of adult cases of paragonimiasis with lung masses as the main manifestation in Xishuangbanna, Yunnan Province, analyze the causes of misdiagnosis, and improve the levels of clinical diagnosis and treatment. METHOD: We conducted a retrospective analysis of the clinical data and diagnosis and treatment of 8 adult cases of paragonimiasis with lung masses as the main manifestation that were diagnosed in the Oncology Department of People's hospital of Xishuangbanna Dai Autonomous Prefecture from July 2014 to July 2019. RESULT: All 8 patients were from epidemic paragonimiasis areas and had a confirmed history of consuming uncooked freshwater crabs. The clinical manifestations were mainly fever, dry cough, and chest pain. The disease durations were long, and peripheral blood eosinophil counts were elevated. The cases had been misdiagnosed as pneumonia or pulmonary tuberculosis. After years of anti-inflammatory or anti-tuberculosis treatment, the symptoms had not improved significantly. Patients eventually sought treatment from the oncology department for hemoptysis. Chest computed tomography showed patchy consolidation in the lungs, with nodules, lung masses, and enlarged mediastinal lymph nodes. CONCLUSION: Paragonimiasis is a food-borne parasitic disease. Early clinical manifestations and auxiliary examination results are nonspecific. The parasite most often invades the lungs, and the resulting disease is often misdiagnosed as pneumonia, pulmonary tuberculosis, or lung cancer (Acta Trop 199: 05074, 2019). To avoid misdiagnosis, clinicians should inquire, in detail, about residence history and history of unclean food and exposure to infected water and make an early diagnosis based on the inquired information and imaging examination results. For patients who have been diagnosed with pneumonia or pulmonary tuberculosis and whose symptoms do not improve significantly after anti-inflammatory or anti-tuberculosis treatments, their epidemiological history should be traced to further conduct differential diagnosis and avoid misdiagnosis.

Small Angle X-ray Scattering Test of Hami Coal Sample Nanostructure Parameters with Gas Adsorbed Under Different Pressures.

The complexity and multiscale structure of coal pores significantly influence the gas diffusion and seepage characteristics of coal. To apply small angle X-ray scattering (SAXS) to study the coal pore structure parameters within the scale of 1-100 nm in the methane adsorption process, the X-ray window was optimized and a gas adsorption chamber was designed to interface with the small angle X-ray scattering platform. The fractal dimension and porosity of Hami coal samples under different methane pressures were studied using the small angle X-ray scattering platform and adsorption chamber. The surface and nanopore fractal information of the nanopores in coal were distinguished. The variation trends of the pores and surface fractal dimension with time under the same methane pressure were compared. The results indicate that the surface dimension changes from 2.56 to 2.75, and the extremum point may indicate that the primary nanopore structure is crushed by the adsorbed gas after approximately 15 minutes. This work clarifies that the fractal dimension can characterize the changes in nanopores in the process of gas adsorption by using SAXS. According to the fractal characteristics, the adsorption of gas in coal nanopores is summarized as four steps: expansion from adsorbance, deformation, crushing and recombination. The minimum porosity is 0.95% and the extreme value point is 1.47%. This work also shows that decrease in surface energy affect the porosity changes in nano-size pores. This work is of some significance to coalbed methane permeability improvement and gas extraction.

Transcriptomics-based identification and characterization of glucosyltransferases involved in betalain biosynthesis in Hylocereus megalanthus.

Pitaya (Hylocereus spp.) is the only commercial cultivation of fruit containing abundant betalains for consumer. Betalains are water-soluble nitrogen-containing pigments with high nutritional value and bioactivities. In this study, contents of betaxanthins and betacyanins were compared between 'Guanhuabai' (H. undatus) and 'Huanglong' (H. megalanthus) pitayas and key genes involved in betalain biosynthesis were screened from 'Huanglong' pitaya by RNA-Seq technology. Twenty-nine candidate genes related to betalain biosynthesis were obtained from the transcriptome data. Based on expression characteristics and sequence analyses, HmB5GT1 and HmHCGT2 were further analyzed. HmB5GT1 and HmHCGT2 were both conserved in 'PSPG-box' and localized in nucleus. Silencing of HmB5GT1 and HmHCGT2 resulted in a significant reduction in betacyanin and betaxanthin contents. Those results suggested that HmB5GT1 and HmHCGT2 are possibly involved in betalain biosynthesis in H. megalanthus. The present work provides new information on betalain biosynthesis in Hylocereus at the transcriptional level.

Genome-wide DNA methylation analysis reveals significant impact of long-term ambient air pollution exposure on biological functions related to mitochondria and immune response.

Exposure to long-term ambient air pollution is believed to have adverse effects on human health. However, the mechanisms underlying these impacts are poorly understood. DNA methylation, a crucial epigenetic modification, is susceptible to environmental factors and likely involved in these processes. We conducted a whole-genome bisulfite sequencing study on 120 participants from a highly polluted region (HPR) and a less polluted region (LPR) in China, where the HPR had much higher concentrations of five air pollutants (PM2.5, PM10, SO2, NO2, and CO) (fold difference 1.6 to 6.6 times; P value 1.80E-07 to 3.19E-23). Genome-wide methylation analysis revealed 371 DMRs in subjects from the two areas and these DMRs were located primarily in gene regulatory elements such as promoters and enhancers. Gene enrichment analysis showed that DMR-related genes were significantly enriched in diseases related to pulmonary disorders and cancers and in biological processes related to mitochondrial assembly and cytokine production. Further, HPR participants showed a higher mtDNA copy number. Of those identified DMRs, 15 were significantly correlated with mtDNA copy number. Finally, cytokine assay indicated that an increased plasma interleukin-5 level was associated with greater air pollution. Taken together, our findings suggest that exposure to long-term ambient air pollution can lead to alterations in DNA methylation whose functions relate to mitochondria and immune responses.

Identification and characterization of SEC24D as a susceptibility gene for hepatitis B virus infection.

Single nucleotide polymorphisms (SNPs) and genes associated with susceptibility to hepatitis B virus (HBV) infection that have been identified by genome-wide association studies explain only a limited portion of the known heritability, indicating more genetic variants remain to be discovered. In this study, we adopted a new research strategy to identify more susceptibility genes and variants for HBV infection. We first performed genetic association analysis of 300 sib-pairs and 3,087 case-control samples, which revealed that 36 SNPs located in 31 genes showed nominal associations with HBV infection in both samples. Of these genes, we selected SEC24D for further molecular analysis according to the following two main lines of evidence. First, a time course analysis of the expression profiles from HBV-infected primary human hepatocytes (PHH) demonstrated that SEC24D expression increased markedly as time passed after HBV infection (P = 4.0 × 10-4). Second, SNP rs76459466 in SEC24D was adversely associated with HBV risk (ORmeta = 0.82; Pmeta = 0.002), which again indicated that SEC24D represents a novel susceptibility gene for HBV infection. Moreover, SEC24D appeared to be protective against HBV infection in vitro. Consistently, we found that SEC24D expression was significantly enhanced in non-infected liver tissues (P = 0.002). We conclude that SEC24D is a novel candidate gene linked to susceptibility to HBV infection.

Detection of Significant Association Between Variants in Cannabinoid Receptor 1 Gene (CNR1) and Personality in African-American Population.

Background: Several studies have revealed significant associations between single nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 (CNR1) gene and a broad spectrum of psychiatric disorders such as major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), and schizophrenia. Personality traits that are highly related to susceptibility to these conditions have been associated with the CNR1 variants in subjects of Caucasian origin. However, there are no reported studies regarding the effects of CNR1 polymorphisms on personality traits in the African-American (AA) population. Methods: We performed an imputation-based association analysis for 26 CNR1 variants with five dimensions of personality in 3,046 AAs. Results: SNPs rs806372 and rs2180619 showed a significant association with extraversion after Bonferroni correction for multiple testing (p < 0.0019). Further, several extraversion-associated SNPs were significantly associated with conscientiousness, agreeableness, and openness. SNP priority score analysis indicated that SNPs rs806368, rs806371, and rs2180619 play a role in the modulation of personality and psychiatric conditions. Conclusion:CNR1 is important in determining personality traits in the AA population.