Publications by authors named "Haiyan Chu"

238 Publications

Identification of common genetic variants associated with serum concentrations of p, p'-DDE in non-occupational populations in eastern China.

Environ Int 2021 Mar 20;152:106507. Epub 2021 Mar 20.

Key Lab of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, PR China; State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, PR China. Electronic address:

Dichlorodiphenyldichloroethylene (DDE) is the major and most stable toxic metabolite of dichlorodiphenyltrichloroethane (DDT), a well-known organochlorine pesticide banned worldwide in the 1980s. However, it remains easy to detect in humans, and internal levels vary widely among individuals. In the present study, a genome-wide association study (GWAS) (511 subjects) and two replications (812 and 1030 subjects) were performed in non-occupational populations in eastern China. An estimated dietary intake (EDI) of p, p'-DDT and p, p'-DDE was calculated by a food frequency questionnaire (FFQ) and the determination of 195 food and 85 drinking water samples. In addition, functional verifications of susceptible loci were performed by dual-luciferase reporter, immunoblotting and metabolic activity assays in vitro. p, p'-DDT and p, p'-DDE were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). A common loci rs3181842 (high linkage equilibrium with rs2279345) in CYP2B6 at 19p13.2 were found to be strongly associated with low serum levels of p, p'-DDE in this population in GWAS and were verified by two replications and combined analysis of 2353 subjects (P = 1.00 × 10). In addition, p, p'-DDE levels were significantly lower in subjects with the rs3181842 C allele than in those carrying the normal genotype, even in individuals with similar EDIs of p, p'-DDT. Furthermore, the rs3181842 C allele functionally led to low CYP2B6 expression and activity, resulting in a low metabolic capacity for the formation of p, p'-DDE from p, p'-DDT. The study highlighted that CYP2B6 variants were more relevant than environmental exposure to internal p, p'-DDE exposure, which is important information for DDT risk assessments.
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http://dx.doi.org/10.1016/j.envint.2021.106507DOI Listing
March 2021

Increasing inundation frequencies enhance the stochastic process and network complexity of soil archaeal community in coastal wetlands.

Appl Environ Microbiol 2021 Mar 19. Epub 2021 Mar 19.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, 71 East Beijing Road, Nanjing 210008, China

Coastal wetlands are experiencing frequent flooding because of global climate changes, such as the rising sea level. Despite the key role of archaea in soil biogeochemical cycles, the assembly processes and co-occurrence patterns of archaeal communities in coastal wetlands in response to increasing inundation frequencies remain elusive. Herein, we established an mesocosm with an inundation frequency gradient to investigate the response of soil archaeal community toward increasing inundation frequencies in monocultures of (SA) and a mangrove species, (KO). Both neutral community model and null model analyses suggested that stochastic processes are dominant in governing the archaeal community assembly, and that the stochastic processes are enhanced with increasing inundation frequencies. Increasing inundation frequencies significantly increased the community niche width. Moreover, archaeal community in SA soil displayed lower niche overlap and higher stochasticity than in KO soil. Co-occurrence network analysis revealed that the network complexity increases with increase in the inundation frequencies. Soil water content is the most decisive factor influencing the archaeal communities. Overall, we found that increasing inundation frequencies enhance the stochastic processes and network complexity of the soil archaeal community in coastal wetlands. This study could enhance our understanding on the response of soil archaeal communities in coastal wetlands toward global change.Coastal wetlands, subjected to regular disturbances by periodic tidal, are highly productive and important in the regulation of climate change. However, the assembly mechanisms and co-occurrence patterns of soil archaeal communities in coastal areas remain poorly known, especially for their responses to increasing inundation frequencies. In this study, we aim at unravelling these uncertainties by studying typical estuarine ecosystems in southern China. We show that increasing inundation frequencies enhance the stochastic processes and network complexity of the soil archaeal community. This study offers a new path for an improved understanding of archaeal community assembly and species coexistence in coastal environments, with a special focus on the role of inundation frequency.
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http://dx.doi.org/10.1128/AEM.02560-20DOI Listing
March 2021

METTL3 regulates PM-induced cell injury by targeting OSGIN1 in human airway epithelial cells.

J Hazard Mater 2021 Mar 3;415:125573. Epub 2021 Mar 3.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address:

N-methyladenosine (mA) is implicated in alteration of cellular biological processes caused by exogenous environmental factors. However, little is known about the role of mA in airborne fine particulate matter (PM)-induced adverse effects. Thus, we investigated the role of mA modification in PM-induced airway epithelial cell injury. We observed a methyltransferase-like 3 (METTL3)-dependent induction of mA modification after PM treatment in HBE and A549 cells. METTL3 knockdown attenuated PM-induced apoptosis and arrest of cell cycle. mRNA sequencing and RNA N-methyladenosine binding protein immunoprecipitation (Me-RIP) assay identified mA-modified oxidative stress induced growth inhibitor 1 (OSGIN1) as the target gene of METTL3. Knockdown of METTL3 resulted a shorter mRNA half-life of OSGIN1 by catalyzing its mA modification. Knockdown of METTL3 or OSGIN1 attenuated cell apoptosis, arrest of cell cycle and autophagy induced by PM. In conclusion, METTL3 may mediate PM-induced cell injury by targeting OSGIN1 in human airway epithelial cells. Our work uncovered a critical role of METTL3 in PM-induced airway epithelial cell injury and provided insight into the vital role of mA modification in PM-induced human hazards.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125573DOI Listing
March 2021

Identification of low-frequency variants of UGT1A3 associated with bladder cancer risk by next-generation sequencing.

Oncogene 2021 Apr 3;40(13):2382-2394. Epub 2021 Mar 3.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

Although genome-wide association studies (GWASs) have successfully revealed many common risk variants for bladder cancer, the heritability is still largely unexplained. We hypothesized that low-frequency variants involved in bladder cancer risk could reveal the unexplained heritability. Next-generation sequencing of 113 patients and 118 controls was conducted on 81 genes/regions of known bladder cancer GWAS loci. A two-stage validation comprising 3,350 cases and 4,005 controls was performed to evaluate the effects of low-frequency variants on bladder cancer risk. Biological experiments and techniques, including electrophoretic mobility shift assays, CRISPR/Cas9, RNA-Seq, and bioinformatics approaches, were performed to assess the potential functions of low-frequency variants. The low-frequency variant rs28898617 was located in the first exon of UGT1A3 and was significantly associated with increased bladder cancer risk (odds ratio = 1.50, P = 3.10 × 10). Intriguingly, rs28898617 was only observed in the Asian population, but monomorphism was observed in the European population. The risk-associated G allele of rs28898617 increased UGT1A3 expression, facilitated UGT1A3 transcriptional activity, and enhanced the binding activity. In addition, UGT1A3 deletion significantly inhibited the proliferation, invasion, and migration of bladder cancer cells and xenograft tumor growth. Mechanistically, UGT1A3 induced LAMC2 expression by binding CBP and promoting histone acetylation, which remarkably promoted the progression of bladder cancer. This is the first targeted sequencing study to reveal that the novel low-frequency variant rs28898617 and its associated gene UGT1A3 are involved in bladder cancer development, providing new insights into the genetic architecture of bladder cancer.
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http://dx.doi.org/10.1038/s41388-021-01672-1DOI Listing
April 2021

Microbial Functional Responses Explain Alpine Soil Carbon Fluxes under Future Climate Scenarios.

mBio 2021 02 23;12(1). Epub 2021 Feb 23.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing, China

Soil microorganisms are sensitive to temperature in cold ecosystems, but it remains unclear how microbial responses are modulated by other important climate drivers, such as precipitation changes. Here, we examine the effects of six warming and/or precipitation treatments in alpine grasslands on microbial communities, plants, and soil carbon fluxes. These treatments differentially affected soil carbon fluxes, gross primary production, and microbial communities. Variations of soil CO and CH fluxes across all sites significantly (>0.70, < 0.050) correlated with relevant microbial functional abundances but not bacterial or fungal abundances. Given tight linkages between microbial functional traits and ecosystem functionality, we conclude that future soil carbon fluxes in alpine grasslands can be predicted by microbial carbon-degrading capacities. The warming pace in the Tibetan Plateau, which is predominantly occupied by grassland ecosystems, has been 0.2°C per decade in recent years, dwarfing the rate of global warming by a factor of 2. Many Earth system models project substantial carbon sequestration in Tibet, which has been observed. Here, we analyzed microbial communities under projected climate changes by 2100. As the soil "carbon pump," the growth and activity of microorganisms can largely influence soil carbon dynamics. However, microbial gene response to future climate scenarios is still obscure. We showed that the abundances of microbial functional genes, but not microbial taxonomy, were correlated with carbon fluxes and ecosystem multifunctionality. By identifying microbial traits linking to ecosystem functioning, our results can guide the assessment of future soil carbon fluxes in alpine grasslands, a critical step toward mitigating climate changes.
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http://dx.doi.org/10.1128/mBio.00761-20DOI Listing
February 2021

Effect of PM exposure on circulating fibrinogen and IL-6 levels: A systematic review and meta-analysis.

Chemosphere 2021 May 7;271:129565. Epub 2021 Jan 7.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address:

Background: Ambient fine particulate matter (PM) pollution poses a great threat on global health. Previous studies have reported that PM regulates circulating fibrinogen and IL-6 levels in the development of cardiovascular and respiratory disease. However, the correlation between PM exposure and both biomarkers remains inconsistent.

Methods: We searched related articles through PubMed, Web of Science and ScienceDirect. Random effects model was used to obtain a pooled estimate effect of both biomarkers as PM concentration increased by every 10 μg/m. Meta-regression analysis, sensitivity analysis and publication bias test were conducted to evaluate the heterogeneity, stability and reliability of this meta-analysis.

Results: A total of 22 articles were included. Each 10 μg/m increase in PM concentration was significantly correlated with a 1.76% increase in circulating fibrinogen level (95% CI: 0.38%-3.14%, P = 0.013) and a 4.66% increase in IL-6 level (95% CI: 1.14%-8.18%, P = 0.010). Subgroup analysis revealed that high-level PM exposure had a more significant association with circulating IL-6 level (11.67%, 95% CI: 0.66%-22.69%, P = 0.038) than low-level exposure, but this association was not observed in fibrinogen (2.50%, 95% CI: -0.78%-5.77%, P = 0.135). Sensitivity analysis and publication bias test confirmed the stability of the results.

Conclusion: Circulating fibrinogen and IL-6 significantly increased with exposure to PM, may serve as promising biomarkers for PM-related adverse effects.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129565DOI Listing
May 2021

The spatial variation of soil bacterial community assembly processes affects the accuracy of source tracking in ten major Chinese cities.

Sci China Life Sci 2021 Jan 8. Epub 2021 Jan 8.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, 210008, China.

Urban soils harbor billions of bacterial cells and millions of species. However, the distribution patterns and assembly processes of bacterial communities remain largely uncharacterized in urban soils. It is also unknown if we can use the bacteria to track soil sources to certain cities and districts. Here, Illumina MiSeq sequencing was used to survey soil bacterial communities from 529 random plots spanning 61 districts and 10 major cities in China. Over a 3,000 km range, community similarity declined with increasing geographic distance (Mantel r=0.62), and community composition was clustered by city (R=0.50). Within cities (<100 km), the aforementioned biogeographic patterns were weakened. Process analysis showed that homogenizing dispersal and dispersal limitation dominated soil bacterial assembly at small and large spatial scales, respectively. Accordingly, the probabilities of accurately tracking random soil sources to certain cities and districts were 90.0% and 66.7%, respectively. When the tested samples originated from cities that were more than 1,265 km apart, the soil sources could be identified with nearly 100% accuracy. Overall, this study demonstrates the strong distance-decay relationship and the clear geographic zoning of urban soil bacterial communities among cities. The varied importance of different community assembly processes at multiple spatial scales strongly affects the accuracy of microbial source tracking.
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http://dx.doi.org/10.1007/s11427-020-1843-6DOI Listing
January 2021

Genetic variants in mA regulators are associated with gastric cancer risk.

Arch Toxicol 2021 03 4;95(3):1081-1088. Epub 2021 Jan 4.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

N-methyladenosine (mA) modification plays a vital regulatory role in tumorigenesis and development. In this study, we determined that the mRNA expression of IGF2BP1, IGF2BP2 and IGF2BP3, as the mA modification genes, was significantly increased in gastric cancer (GC) tissues. Using a logistic regression model, we found that novel single-nucleotide polymorphism (SNP) rs9906944 C > T in IGF2BP1 was remarkably associated with a decreased risk of GC in discovery stage (odds ratio (OR) = 0.75, 95% confidence interval (95% CI): 0.60-0.93, P = 8.51 × 10). This finding was repeated in an independent Nanjing population (OR = 0.76, 95% CI: 0.59-0.98, P = 3.45 × 10). The combined analysis including 2900 GC cases and 3,536 controls confirmed the association between rs9906944 C > T and GC risk (OR = 0.75, 95% CI: 0.64-0.88, P = 5.76 × 10). Furthermore, we found that GC patients with higher IGF2BP1 mRNA expression level had prominent poorer overall survival (hazard ratio (HR) = 1.49, 95% CI: 1.16-1.91, logrank P = 1.50 × 10). For the first time, our findings suggested the importance of genetic variants in mA regulators in GC and indicated that IGF2BP1 plays a crucial role in GC. Genetic variants in mA modification genes may be used for GC risk prediction.
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http://dx.doi.org/10.1007/s00204-020-02958-1DOI Listing
March 2021

Distinct Community Assembly Processes of Abundant and Rare Soil Bacteria in Coastal Wetlands along an Inundation Gradient.

mSystems 2020 Dec 22;5(6). Epub 2020 Dec 22.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, China

Microbial communities commonly consist of a large number of rare taxa (RT) and few abundant taxa (AT), and it is important to identify the differences of the community assembly processes between RT and AT in response to environmental changes. However, the community assembly processes governing AT and RT in coastal wetland soils along an inundation gradient remain elusive. Here, an mesocosm, with continuous inundation gradients and native mangrove or exotic cordgrass , was established to determine the patterns and driving factors of community turnover and assembly processes of AT and RT. We found that RT exhibited a remarkably lower turnover rate than AT, and the niche breadth of RT was significantly narrower than that of AT. In comparison with AT, RT presented stronger phylogenetic signals for ecological preferences across environmental gradients. Null model analyses revealed that RT were more phylogenetically clustered and primarily governed by homogeneous selection, while AT were more overdispersed and dominated by dispersal limitation. Soil water content was the most decisive factor for community turnover and assembly processes of both AT and RT. Structural equation modeling analysis showed that RT were strongly associated with biomass rather than biomass, suggesting a strong relationship between RT and the growth of mangrove Overall, our study revealed distinct assembly processes of soil AT and RT communities in coastal wetlands, which is crucial for mechanistic understanding of the establishment and maintenance of soil microbial diversity in coastal wetlands under conditions of global environmental changes. Coastal wetlands are one of the important ecosystems that play a crucial role in the regulation of climate change. Rare taxa (RT) exist in one habitat along with abundant taxa (AT). In this study, we found that RT exhibited narrower niche breadth and stronger phylogenetic signals than AT. Null model analyses showed that RT were more phylogenetically clustered and primarily governed by homogeneous selection, while AT were more overdispersed and dominated by dispersal limitation. Revealing the differences in the community assembly processes between AT and RT in coastal wetlands is critical to understand the establishment and maintenance of soil microbial diversity in coastal wetlands with regard to environmental changes.
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http://dx.doi.org/10.1128/mSystems.01150-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762797PMC
December 2020

A prospective study of the associations among fine particulate matter, genetic variants, and the risk of colorectal cancer.

Environ Int 2021 Feb 15;147:106309. Epub 2020 Dec 15.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address:

Background: Fine particulate matter (PM) is suspected to increase the risk of colorectal cancer, but the mechanism remains unknown. We aimed to investigate the association between PM exposure, genetic variants and colorectal cancer risk in the Prostate, Lung, Colon and Ovarian (PLCO) Cancer Screening trial.

Methods: We included a prospective cohort of 139,534 cancer-free individuals from 10 United States research centers with over ten years of follow-up. We used a Cox regression model to assess the association between PM exposure and colorectal cancer incidence by calculating the hazard ratio (HR) and 95% confidence interval (CI) with adjustment for potential confounders. The polygenic risk score (PRS) and genome-wide interaction analysis (GWIA) were used to evaluate the multiplicative interaction between PM exposure and genetic variants in regard to colorectal cancer risk.

Results: After a median of 10.43 years of follow-up, 1,666 participants had been diagnosed with colorectal cancer. PM exposure was significantly associated with an increased risk of colorectal cancer (HR = 1.27; 95% CI = 1.17-1.37 per 5 μg/m increase). Five independent susceptibility loci reached statistical significance at P < 1.22 × 10 in the interaction analysis. Furthermore, a joint interaction was observed between PM exposure and the PRS based on these five loci with colorectal cancer risk (P = 3.11 × 10). The Gene Ontology analysis showed that the vascular endothelial growth factor (VEGF) receptor signaling pathway was involved in the biological process of colorectal cancer.

Conclusions: Our large-scale analysis has shown for the first time that long-term PM exposure potential increases colorectal cancer risk, which might be modified by genetic variants.
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http://dx.doi.org/10.1016/j.envint.2020.106309DOI Listing
February 2021

Systematic evaluation of the effects of genetic variants on PIWI-interacting RNA expression across 33 cancer types.

Nucleic Acids Res 2021 01;49(1):90-97

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

PIWI-interacting RNAs (piRNAs) are an emerging class of non-coding RNAs involved in tumorigenesis. Expression quantitative trait locus (eQTL) analysis has been demonstrated to help reveal the genetic mechanism of single nucleotide polymorphisms (SNPs) in cancer etiology. However, there are no databases that have been constructed to provide an eQTL analysis between SNPs and piRNA expression. In this study, we collected genotyping and piRNA expression data for 10 997 samples across 33 cancer types from The Cancer Genome Atlas (TCGA). Using linear regression cis-eQTL analysis with adjustment of appropriate covariates, we identified millions of SNP-piRNA pairs in tumor (76 924 831) and normal (24 431 061) tissues. Further, we performed differential expression and survival analyses, and linked the eQTLs to genome-wide association study (GWAS) data to comprehensively decipher the functional roles of identified cis-piRNA eQTLs. Finally, we developed a user-friendly database, piRNA-eQTL (http://njmu-edu.cn:3838/piRNA-eQTL/), to help users query, browse and download corresponding eQTL results. In summary, piRNA-eQTL could serve as an important resource to assist the research community in understanding the roles of genetic variants and piRNAs in the development of cancers.
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http://dx.doi.org/10.1093/nar/gkaa1190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797066PMC
January 2021

Metabolomics identifying biomarkers of PM exposure for vulnerable population: based on a prospective cohort study.

Environ Sci Pollut Res Int 2021 Mar 19;28(12):14586-14596. Epub 2020 Nov 19.

State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Road, Nanjing, 211198, China.

Long-term exposure to particular matter (PM), especially fine PM (< 2.5 μm in the aerodynamic diameter, PM), is associated with increased risk of cardiovascular disorders. This study aimed to evaluate the association between long-term exposure to PM/PM and the metabolic change in the plasma. Specifically, using metabolomics, we sought to identify the biomarkers for the vulnerable subgroup to PM exposure. A total of 78 college student volunteers were recruited into this prospective cohort study. All participants received 8 rounds of physical examinations at twice quarterly. Air purifiers were placed in 40 of 78 participants' dormitories for 14 days. Before and after intervention, physical examinations were performed and the peripheral blood was collected. Plasma metabolomics was determined by ultra-performance liquid chromatography-mass spectrometry. During the follow-up, the average concentrations of PM and PM were 53 μg/m and 93 μg/m, respectively. Totally, 42 and 120 differential metabolic features were detected for PM and PM exposure, respectively. In total, 25 differential metabolites were identified for PM exposure, most of which were phospholipids. No distinctive metabolites were found for PM exposure. A total of 6 differential metabolites (lysoPC (P-20:0), lysoPC (P-18:1(9z)), lysoPC (20:1), lysoPC (O-16:0), choline, and found 1,3-diphenylprop-2-en-1-one) were characterized and confirmed for sensitive individuals. Importantly, we found LysoPC (P-20:0) and LysoPC (P-18:1(9z)) changed significantly before and after air purifier intervention. Our results indicated that the phospholipid catabolism was involved in long-term PM exposure. LysoPC (P-20:0) and LysoPC (P-18:1(9z)) may be the biomarkers of PM exposure.
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http://dx.doi.org/10.1007/s11356-020-11677-0DOI Listing
March 2021

Exome-Wide Association Analysis Suggests LRP2BP as a Susceptibility Gene for Endothelial Injury in Systemic Sclerosis in the Han Chinese Population.

J Invest Dermatol 2020 Oct 15. Epub 2020 Oct 15.

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China; Human Phenome Institute, Fudan University, Shanghai, China; Research Unit of dissecting the population genetics and developing new technologies for treatment and prevention of skin phenotypes and dermatological diseases (2019RU058), Chinese Academy of Medical Sciences, Beijing, China; Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China. Electronic address:

Genetic factors play a key role in the pathogenesis of autoimmune diseases, whereas the disease-causing variants remain largely unknown. Herein, we performed an exome-wide association study of systemic sclerosis in a Han Chinese population. In the discovery stage, 527 patients with systemic sclerosis and 5,024 controls were recruited and genotyped. In the validation study, an independent sample set of 479 patients and 1,096 controls were examined. In total, we found that four independent signals reached genome-wide significance. Among them, rs7574865 (P = 3.87 × 10) located within signal transducer and activator of transcription 4 gene was identified previously using samples of European ancestry. Additionally, another signal including three SNPs in linkage disequilibrium might be unreported susceptibility loci located in the epidermis differentiation complex region. Furthermore, two SNPs located within exon 3 of IGHM (rs45471499, P = 1.15 × 10) and upstream of LRP2BP (rs4317244, P = 4.17 × 10) were found. Moreover, rs4317244 was identified as an expression quantitative trait locus for LRP2BP that regulates tight junctions, cell cycle, and apoptosis in endothelial cell lines. Collectively, our results revealed three signals associated with systemic sclerosis in Han Chinese and suggested the importance of LRP2BP in systemic sclerosis pathogenesis. Given the limited sample size and discrepancies between previous results and our study, further studies in multiethnic populations are required for verification.
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http://dx.doi.org/10.1016/j.jid.2020.07.039DOI Listing
October 2020

Dramatic change of bacterial assembly process and co-occurrence pattern in Spartina alterniflora salt marsh along an inundation frequency gradient.

Sci Total Environ 2021 Feb 28;755(Pt 1):142546. Epub 2020 Sep 28.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, 71 East Beijing Road, Nanjing 210008, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Exotic Spartina alterniflora has become widely distributed along most of the coastlines in China in a wide range of inundation frequencies. However, the assembly processes and co-occurrence patterns of the bacterial community in S. alterniflora wetlands under different inundation frequencies remain elusive. In this study, an in-situ mesocosm was established to investigate the changes in soil bacterial community. We found that soil water content was the most decisive factor in influencing the bacterial community. Balanced variation, rather than abundance gradients, accounted for the major shifts in bacterial communities and was significantly and positively correlated with the changes in water content, suggesting that species substitution was facilitated by the increased water content. Deterministic processes were dominant in community assembly, and a large degree of change in water content increased variable selection. Co-occurrence network revealed that increasing water content significantly decreased the average degree and the relative abundance of keystone species, resulting in a network with less complexity. Structural equation modelling suggests that increasing inundation frequency has strong impacts on bacterial community, primarily by altering water content, network degree, and the relative abundance of keystone species. Overall, our results illustrate that increasing inundation frequency significantly influences the bacterial community assembly processes and co-occurrence patterns.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142546DOI Listing
February 2021

Biodiversity of key-stone phylotypes determines crop production in a 4-decade fertilization experiment.

ISME J 2021 Feb 7;15(2):550-561. Epub 2020 Oct 7.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, 71 East Beijing Road, Nanjing, 210008, China.

Cropping systems have fertilized soils for decades with undetermined consequences for the productivity and functioning of terrestrial ecosystems. One of the critical unknowns is the role of soil biodiversity in controlling crop production after decades of fertilization. This knowledge gap limits our capacity to assess how changes in soil biodiversity could alter crop production and soil health in changing environments. Here, we used multitrophic ecological networks to investigate the importance of soil biodiversity, in particular, the biodiversity of key-stone taxa in controlling soil functioning and wheat production in a 35-year field fertilization experiment. We found strong and positive associations between soil functional genes, crop production and the biodiversity of key-stone phylotypes; soils supporting a larger number of key-stone nematode, bacteria and fungi phylotypes yielded the highest wheat production. These key-stone phylotypes were also positively associated with plant growth (phototrophic bacteria, nitrogen fixers) and multiple functional genes related to nutrient cycling. The retrieved information on the genomes clustered with key-stone bacterial phylotypes indicated that the key-stone taxa had higher gene copies of oxidoreductases (participating most biogeochemical cycles of ecosystems and linking to microbial energetics) and 71 essential functional genes associated with carbon, nitrogen, phosphorus, and sulfur cycling. Altogether, our work highlights the fundamental role of the biodiversity of key-stone phylotypes in maintaining soil functioning and crop production after several decades of fertilization, and provides a list of key-stone phylotypes linking to crop production and soil nutrient cycling, which could give science-based guidance for sustainable food production.
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http://dx.doi.org/10.1038/s41396-020-00796-8DOI Listing
February 2021

Genetic variants in N6-methyladenosine are associated with bladder cancer risk in the Chinese population.

Arch Toxicol 2021 01 22;95(1):299-309. Epub 2020 Sep 22.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.

Recently N-Methyladenosine (mA) has been identified to guide the interaction of RNA-binding protein hnRNP C and their target RNAs, which is termed as mA-switches. We systematically investigated the association between genetic variants in mA-switches and bladder cancer risk. A two-stage case-control study was performed to systematically calculate the association of single nucleotide polymorphisms (SNPs) in 2798 mA-switches with bladder cancer risk in 3,997 subjects. A logistic regression model was used to assess the effects of SNPs on bladder cancer risk. A series of experiments were adopted to explore the role of genetic variants of mA-switches. We identified that rs5746136 (G > A) of SOD2 in mA-switches was significantly associated with the reduced risk of bladder cancer (additive model in discovery stage: OR = 0.80, 95% CI 0.69-0.93, P = 3.6 × 10; validation stage: adjusted OR = 0.88, 95% CI 0.79-0.99, P = 3.0 × 10; combined analysis: adjusted OR = 0.85, 95% CI 0.78-0.93, P = 4.0 × 10). The mRNA level of SOD2 was remarkably lower in bladder cancer tissues than the paired adjacent samples. SNP rs5746136 may affect mA modification and regulate SOD2 expression by guiding the binding of hnRNP C to SOD2, which played a critical tumor suppressor role in bladder cancer cells by promoting cell apoptosis and inhibiting proliferation, migration and invasion. In conclusion, our findings suggest the important role of genetic variants in mA modification. SOD2 polymorphisms may influence the expression of SOD2 via an mA-hnRNP C-dependent mechanism and be promising predictors of bladder cancer risk.
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http://dx.doi.org/10.1007/s00204-020-02911-2DOI Listing
January 2021

Relationship between particulate matter exposure and female breast cancer incidence and mortality: a systematic review and meta-analysis.

Int Arch Occup Environ Health 2021 Feb 10;94(2):191-201. Epub 2020 Sep 10.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Jiangning District, Nanjing, 211166, China.

Objectives: The associations of PM with the risk and prognosis of breast cancer have not been determined. This systematic review aimed to provide an updated understanding of the relationship between PM exposure level and breast cancer incidence and mortality.

Methods: Articles from Web of Science and PubMed databases were methodically inspected until March 8, 2020. In final, 15 studies were kept for analysis, which provided necessary information to estimate the impact of PM on breast cancer risk and prognosis. These studies were combined for quantitative analyses to evaluate the effect of per 10 μg /m increment exposure of PM (< 2.5 μm in aerodynamic diameter) and PM (< 10 μm in aerodynamic diameter) using random-effects model.

Results: PM exposure was associated with increased breast cancer mortality (relative risk [RR] = 1.09; 95% confidence interval [CI]: 1.02, 1.16; P = 0.158). No association of PM (1.02; 0.97, 1.18; 0.308) and PM (1.03; 0.98, 1.09; 0.009) with the increase incidence of breast cancer was observed. Stratified analysis suggested that PM was associated with the increase mortality of breast cancer (1.10; 1.03, 1.17; 0.529) in subgroup of developed country. PM was associated with breast cancer incidence based on studies published after 2017 (1.08; 1.00, 1.15; 0.157) and European studies (1.15; 1.06, 1.25; 0.502).

Conclusions: Our study indicated that PM exposure was related to breast cancer mortality. Further researches in this field are needed to validate the conclusion.
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http://dx.doi.org/10.1007/s00420-020-01573-yDOI Listing
February 2021

Remote modulation of lncRNA by risk variant at 16p13 underlying genetic susceptibility to gastric cancer.

Sci Adv 2020 May 20;6(21):eaay5525. Epub 2020 May 20.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

The biological effects of susceptibility loci are rarely reported in gastric tumorigenesis. We conducted a large-scale cross-ancestry genetic study in 18,852 individuals and identified the potential causal variant rs3850997 T>G at 16p13 significantly associated with a decreased risk of gastric cancer [odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.83 to 0.91, = 2.13 × 10]. This risk effect was mediated through the mapped long noncoding RNA (; OR = 0.987, 95% CI = 0.975 to 0.999, = 0.018). Mechanistically, rs3850997 exerted an allele-specific long-range regulatory effect on by affecting the binding affinity of CTCF. Furthermore, increased expression by competing with miR-27a-3p, and this regulation remarkably affected in vitro, in vivo, and clinical gastric cancer phenotypes. The findings highlight the genetic functions and implications for the etiology and pathology of cancers.
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http://dx.doi.org/10.1126/sciadv.aay5525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314563PMC
May 2020

A transcriptomic study for identifying cardia- and non-cardia-specific gastric cancer prognostic factors using genetic algorithm-based methods.

J Cell Mol Med 2020 08 10;24(16):9457-9465. Epub 2020 Jul 10.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.

Gastric cancer (GC) is a heterogeneous tumour with numerous differences of epidemiologic and clinicopathologic features between cardia cancer and non-cardia cancer. However, few studies were performed to construct site-specific GC prognostic models. In this study, we identified site-specific GC transcriptomic prognostic biomarkers using genetic algorithm (GA)-based support vector machine (GA-SVM) and GA-based Cox regression method (GA-Cox) in the Cancer Genome Atlas (TCGA) database. The area under time-dependent receive operating characteristic (ROC) curve (AUC) regarding 5-year survival and concordance index (C-index) was used to evaluate the predictive ability of Cox regression models. Finally, we identified 10 and 13 prognostic biomarkers for cardia cancer and non-cardia cancer, respectively. Compared to traditional models, the addition of these site-specific biomarkers could notably improve the model preference (cardia: AUC vs AUC  = 0.720 vs 0.899, P = 8.75E-08; non-cardia: AUC vs AUC  = 0.798 vs 0.994, P = 7.11E-16). The combined nomograms exhibited superior performance in cardia and non-cardia GC survival prediction (C-index  = 0.816; C-index  = 0.812). We also constructed a user-friendly GC site-specific molecular system (GC-SMS, https://njmu-zhanglab.shinyapps.io/gc_sms/), which is freely available for users. In conclusion, we developed site-specific GC prognostic models for predicting cardia cancer and non-cardia cancer survival, providing more support for the individualized therapy of GC patients.
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http://dx.doi.org/10.1111/jcmm.15618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417703PMC
August 2020

Abundance of kinless hubs within soil microbial networks are associated with high functional potential in agricultural ecosystems.

Environ Int 2020 09 25;142:105869. Epub 2020 Jun 25.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, 71 East Beijing Road, Nanjing 210008, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Microbial taxa within complex ecological networks can be classified by their universal roles based on their level of connectivity with other taxa. Highly connected taxa within an ecological network (kinless hubs) are theoretically expected to support higher levels of ecosystem functions than less connected taxa (peripherals). Empirical evidence of the role of kinless hubs in regulating the functional potential of soil microbial communities, however, is largely unexplored and poorly understood in agricultural ecosystems. Here, we built a correlation network of fungal and bacterial taxa using a large-scale survey consisting of 243 soil samples across functionally and economically important agricultural ecosystems (wheat and maize); and found that the relative abundance of taxa classified as kinless hubs within the ecological network are positively and significantly correlated with the abundance of functional genes including genes for C fixation, C degradation, C methanol, N cycling, P cycling and S cycling. Structural equation modeling of multiple soil properties further indicated that kinless hubs, but not provincial, connector or peripheral taxa, had direct significant and positive relationships with the abundance of multiple functional genes. Our findings provide novel evidence that the relative abundance of soil taxa classified as kinless hubs within microbial networks are associated with high functional potential, with implications for understanding and managing (through manipulating microbial key species) agricultural ecosystems at a large spatial scale.
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http://dx.doi.org/10.1016/j.envint.2020.105869DOI Listing
September 2020

Genetic variants in Ras/Raf/MEK/ERK pathway are associated with gastric cancer risk in Chinese Han population.

Arch Toxicol 2020 08 11;94(8):2683-2690. Epub 2020 Jun 11.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

The dysregulation of Ras/Raf/MEK/ERK pathway governs occurrence and progression of cancers. In previous studies, genome-wide association studies (GWAS) have identified multiple gene loci related to gastric cancer. However, a great many genetic loci have been missed due to multiple statistical comparisons of GWAS. In this study, Multi-marker Analysis of GenoMic Annotation (MAGMA) was applied to analyze genes in Ras/Raf/MEK/ERK pathway and their single nucleotide polymorphisms (SNPs) based on Chinese GWAS including 1625 gastric cancer cases and 2100 controls. The SNP effects on gastric cancer susceptibility were calculated on the basis of a logistic regression model. Expression quantitative trait loci (eQTL) analysis was performed based on the genotype-tissue expression (GTEx) project. We identified that three SNPs in MAP2K1, rs4287513, rs76906202 and rs11631448 were markedly associated with gastric cancer risk (rs4287513: OR = 1.30, 95% CI = 1.10-1.54, P = 1.92 × 10; rs76906202: OR = 0.87, 95% CI = 0.79-0.96, P = 3.72 × 10; rs11631448: OR = 1.21, 95% CI = 1.05-1.39, P = 6.74 × 10). All the loci were eQTLs for MAP2K1 in normal gastric samples. Moreover, the low expression of MAP2K1 was significantly associated with poor survival in gastric cancer patients. Thus, MAP2K1 might represent a key gene related to gastric cancer in Ras/Raf/MEK/ERK pathway, whereas SNPs in MAP2K1 confer gastric cancer susceptibility by having biological effects on the MAP2K1 expression.
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http://dx.doi.org/10.1007/s00204-020-02771-wDOI Listing
August 2020

Space Is More Important than Season when Shaping Soil Microbial Communities at a Large Spatial Scale.

mSystems 2020 May 12;5(3). Epub 2020 May 12.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, China

The relative importance of spatial and temporal variability in shaping the distribution of soil microbial communities at a large spatial scale remains poorly understood. Here, we explored the relative importance of space versus time when predicting the distribution of soil bacterial and fungal communities across North China Plain in two contrasting seasons (summer versus winter). Although we found that microbial alpha (number of phylotypes) and beta (changes in community composition) diversities differed significantly between summer and winter, space rather than season explained more of the spatiotemporal variation of soil microbial alpha and beta diversities. Environmental covariates explained some of microbial spatiotemporal variation observed, with fast-changing environmental covariates-climate variables, soil moisture, and available nutrient-likely being the main factors that drove the seasonal variation found in bacterial and fungal beta diversities. Using random forest modeling, we further identified a group of microbial exact sequence variants (ESVs) as indicators of summer and winter seasons and for which relative abundance was associated with fast-changing environmental variables (e.g., soil moisture and dissolved organic nitrogen). Together, our empirical field study's results suggest soil microbial seasonal variation could arise from the changes of fast-changing environmental variables, thus providing integral support to the large emerging body of snapshot studies related to microbial biogeography. Both space and time are key factors that regulate microbial community, but microbial temporal variation is often ignored at a large spatial scale. In this study, we compared spatial and seasonal effects on bacterial and fungal diversity variation across an 878-km transect and found direct evidence that space is far more important than season in regulating the soil microbial community. Partitioning the effect of season, space and environmental variables on microbial community, we further found that fast-changing environmental factors contributed to microbial temporal variation.
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http://dx.doi.org/10.1128/mSystems.00783-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219554PMC
May 2020

Alternative splicing related genetic variants contribute to bladder cancer risk.

Mol Carcinog 2020 08 27;59(8):923-929. Epub 2020 Apr 27.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

Emerging evidence has shown that aberrant alternative splicing (AS) events are involved in the carcinogenesis. The association between genetic variants in AS and bladder cancer susceptibility remains to be fully elucidated. We searched for single nucleotide polymorphisms (SNPs) which are located in splicing quantitative trait loci (sQTLs) in bladder cancer through CancerSplicingQTL database and the 1000 Genomes Project. A case-control study including 580 cases and 1,101 controls was conducted to assess the association between the functional genetic variants and bladder cancer risk. Next, we used GTEx, TCGA, and GEO databases conducting sQTL analysis and gene expression differences analysis to evaluate the potential biological function of the candidate SNPs and related genes. We found that SNP rs4383 C>G was remarkably related with the reduced risk of bladder cancer (odds ratio = 0.68, 95% confidence interval = 0.59-0.79, P = 3.91 × 10 ). Similar results were obtained in codominant, dominant and recessive model. Stratified analyses revealed that the effect of SNP rs4383 C>G on bladder cancer was more significant in the older subjects (age > 65), female and nonsmokers. sQTL analysis showed that SNP rs4383 was associated with the AS events of its downstream gene MAFF with a splicing event of alternative 5' splice site. The messenger RNA expression of MAFF in bladder tumor tissues was lowered compared with normal tissues. Patients with high expression of MAFF had higher survival rates. These findings indicated that SNP rs4383 related with the AS events of MAFF was associated with bladder cancer risk and could represent a possible biomarker for bladder cancer susceptibility.
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http://dx.doi.org/10.1002/mc.23207DOI Listing
August 2020

Microbes changed their carbon use strategy to regulate the priming effect in an 11-year nitrogen addition experiment in grassland.

Sci Total Environ 2020 Jul 16;727:138645. Epub 2020 Apr 16.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, 71 East Beijing Road, Nanjing 210008, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Nitrogen availability is a key factor that regulates soil priming (the strong short-term changes in microbial decomposition of soil organic carbon after addition of fresh carbon resources); however, how soil priming changes under nitrogen addition is unclear. In this study, we collected soils from a grassland with 11-year history of nitrogen addition (0, 60, 120, and 240 kg N ha yr NHNO), and the soils were incubated for 6 weeks to estimate the direction and magnitude of soil priming and the underlying microbial carbon use strategy. We found glucose addition triggered a positive priming effect among all the treatments; however, the magnitude of the positive priming did not change under nitrogen addition. The stable soil organic carbon content under different nitrogen addition levels might support the no significant change in the magnitude of those positive priming. Using DNA stable-isotope probing (DNA-SIP), we found that bacterial and fungal taxa consuming the added glucose were different in different nitrogen addition levels. The relative abundance of the K-strategist Acidobacteria increased with increasing nitrogen addition levels, while the r-strategist Firmicutes decreased with increasing nitrogen addition levels. Our results indicated microbial taxa exhibited carbon use plasticity, with most taxa altering their use of glucose under nitrogen addition.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138645DOI Listing
July 2020

Soil Microbial Biogeography in a Changing World: Recent Advances and Future Perspectives.

mSystems 2020 Apr 21;5(2). Epub 2020 Apr 21.

Departamento de Sistemas Físicos, Químicos y Naturales, Universidad Pablo de Olavide, Seville, Spain

Soil microbial communities are fundamental to maintaining key soil processes associated with litter decomposition, nutrient cycling, and plant productivity and are thus integral to human well-being. Recent technological advances have exponentially increased our knowledge concerning the global ecological distributions of microbial communities across space and time and have provided evidence for their contribution to ecosystem functions. However, major knowledge gaps in soil biogeography remain to be addressed over the coming years as technology and research questions continue to evolve. In this minireview, we state recent advances and future directions in the study of soil microbial biogeography and discuss the need for a clearer concept of microbial species, projections of soil microbial distributions toward future global change scenarios, and the importance of embracing culture and isolation approaches to determine microbial functional profiles. This knowledge will be critical to better predict ecosystem functions in a changing world.
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http://dx.doi.org/10.1128/mSystems.00803-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174637PMC
April 2020

Distinct fungal successional trajectories following wildfire between soil horizons in a cold-temperate forest.

New Phytol 2020 07 14;227(2):572-587. Epub 2020 Apr 14.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, East Beijing Road 71, Nanjing, 210008, China.

Soil fungi represent a major component of below-ground biodiversity that determines the succession and recovery of forests after disturbance. However, their successional trajectories and driving mechanisms following wildfire remain unclear. We examined fungal biomass, richness, composition and enzymes across three soil horizons (Oe, A1 and A2) along a near-complete fire chronosequence (1, 2, 8, 14, 30, 49 and c. 260 yr) in cold-temperate forests of the Great Khingan Mountains, China. The importance of soil properties, spatial distance and tree composition were also tested. Ectomycorrhizal fungal richness and β-glucosidase activity were strongly reduced by burning and significantly increased with 'time since fire' in the Oe horizon but not in the mineral horizons. Time since fire and soil C : N ratio were the primary drivers of fungal composition in the Oe and A1/A2 horizons, respectively. Ectomycorrhizal fungal composition was remarkably sensitive to fire history in the Oe horizon, while saprotroph community was strongly affected by time since fire in the deeper soil horizon and this effect emerged 18 years after fire in the A2 horizon. Our study demonstrates pronounced horizon-dependent successional trajectories following wildfire and indicates interactive effects of time since fire, soil stoichiometry and spatial distance in the reassembly of below-ground fungal communities in a cold and fire-prone region.
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http://dx.doi.org/10.1111/nph.16531DOI Listing
July 2020

Long-Term Phytoremediation of Coastal Saline Soil Reveals Plant Species-Specific Patterns of Microbial Community Recruitment.

mSystems 2020 Mar 3;5(2). Epub 2020 Mar 3.

Key Laboratory of Agricultural Water Resources, Hebei Key Laboratory of Soil Ecology, Center for Agricultural Resources Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Shijiazhuang, China

Soil salinization is one of the major land degradation processes that decreases soil fertility and crop production worldwide. In this study, a long-term coastal saline soil remediation experiment was conducted with three salt-tolerant plant species: Mill. (LCM), Lour. (TCL), and Linn. (GHL). The three plant species successfully remediated the saline soil but showed different efficacies. The archaeal, bacterial, and fungal communities in barren soil and in four rhizocompartments (distal-rhizosphere soil, proximal-rhizosphere soil, rhizoplane, and endosphere) of the three plant species were assessed. All three plant species significantly decreased the richness of the archaeal communities but increased that of the bacterial and fungal communities in both the rhizosphere and rhizoplane compared with those in the barren soil. The archaeal and bacterial community structures were strongly influenced by the rhizocompartment, while specific fungal communities were recruited by different plant species. The microbial taxa whose abundance either increased or decreased significantly during remediation were identified. Soil electrical conductivity (EC) was identified as the main factor driving the variation in microbial community composition between the remediated and barren soil, and total nitrogen (TN), total carbon (TC), and available potassium (AK) were the main factors driving the differences among plant species. This report provides new insights into the responses of the root zone microbial communities of different salt-tolerant plant species during phytoremediation. Despite knowing that phytoremediation by salt-tolerant plants is an effective technology for ameliorating saline soils and that microorganisms contribute significantly to plant stress tolerance and soil fertility, we still lack a comprehensive understanding of how microbes respond to the growth of salt-tolerant plants and the subsequent decline in soil salinity. The results of this study revealed different response patterns among bacterial, archaeal, and fungal communities and indicated that the decline in archaeal abundance might be a sign of successful remediation of coastal saline soils. The recruitment of specific fungal communities by different plant species indicated the importance of fungi in plant species-specific remediation functions. We also identified the taxa that may play key roles during remediation, and these taxa could potentially be used as indicators of phytoremediation. Overall, these findings highlight the importance of microbes in the phytoremediation of saline soil and suggest that the mechanisms involved are plant species specific.
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http://dx.doi.org/10.1128/mSystems.00741-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055657PMC
March 2020

Genetic variations in Hippo pathway genes influence bladder cancer risk in a Chinese population.

Arch Toxicol 2020 03 2;94(3):785-794. Epub 2020 Mar 2.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, Jiangsu, China.

The Hippo pathway participates in development of numerous tumors through regulating tissue growth and cell fate. This study aimed to detect the association between the genetic variants in Hippo pathway genes and bladder cancer risk in a Chinese population. A case-control study of 580 cases and 1101 controls was performed to evaluate the association of single nucleotide polymorphisms (SNPs) in 39 candidate genes involved in the Hippo pathway with bladder cancer risk. A logistic regression model was used to assess the effects of SNPs on bladder cancer susceptibility. Candidate gene expression in human bladder cancer samples was detected using The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) datasets. We found that SNP rs755813 in WWC1 was significantly associated with a decreased risk of bladder cancer [odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.66-0.88, P = 3.63 × 10], which was more common in patients with low grade and non-muscle invasive tumors. Younger subjects (age ≤ 65) (OR = 0.70, 95% CI = 0.56-0.86), females (0.35, 0.23-0.52) and non-smokers (0.72, 0.58-0.88) showed a pronounced association between the rs755813 C allele and risk of bladder cancer by stratified analysis. The WWC1 was upregulated in bladder cancer tissues according to TCGA and GEO datasets. These findings indicated that genetic variant of WWC1 gene in Hippo signaling pathway contributes to the decreased risk of bladder cancer in the Chinese population and may have the protective effect against the development of bladder cancer.
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http://dx.doi.org/10.1007/s00204-020-02663-zDOI Listing
March 2020

MUC1 is associated with TFF2 methylation in gastric cancer.

Clin Epigenetics 2020 03 2;12(1):37. Epub 2020 Mar 2.

Department of Environmental Genomics, School of Public Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.

Background: Emerging evidence has shown that MUC1 and TFF2 play crucial roles in the H. pylori-infected pathogenesis of gastric cancer (GC). A recent study revealed that H. pylori infection induced obviously increased Tff2 methylation levels in Muc1 mice compared with controls. However, little is known of the molecular mechanism on MUC1 regulating the expression of TFF2.

Methods: We conducted a correlation analysis of MUC1 and TFF2 in public databases and our adjacent GC tissues. Besides, MUC1 overexpression vector or small interfering RNA (siRNA) was transfected into GC cells to assess the change in TFF2 expression. Furthermore, the methylation status of TFF2 was measured by bisulfite sequencing PCR (BSP).

Results: The expression of MUC1 was significantly lower in non-cardia and cardia tumor tissues than that in normal tissues. Downregulation of TFF2 expression was also observed in GC tissues. In addition, we found that MUC1 expression was positively associated with TFF2 expression in GC tissues, especially among GC patients with H. pylori infection. Overexpression of MUC1 in BGC-823 and SGC-7901 cell lines substantially increased the TFF2 expression, whereas knockdown of MUC1 reverted this effect. Moreover, MUC1 was negatively related to the methylation of TFF2 in the co-expression analysis. The results of BSP experiments showed that compared with negative vector group, the methylation level of TFF2 was decreased in GC cells transfected with MUC1 overexpression vector. Additionally, survival analysis indicated that GC patients with lower level of MUC1 or TFF2 had a worse outcome.

Conclusion: Our results indicated that MUC1 was associated with the methylation of TFF2, which may have implications for TFF2 expression in GC. These findings warrant further research toward the underlying mechanism of MUC1 influenced the TFF2 methylation.
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http://dx.doi.org/10.1186/s13148-020-00832-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053135PMC
March 2020

Sex hormones and genetic variants in hormone metabolic pathways associated with the risk of colorectal cancer.

Environ Int 2020 04 18;137:105543. Epub 2020 Feb 18.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address:

Objective: The different incidence of colorectal cancer between the sexes suggests that sex hormones may be involved in the susceptibility to colorectal cancer. The association between sex hormones and genetic variants in hormone metabolic pathways and the colorectal cancer risk remains unclear.

Methods: We detected sex hormone levels in plasma from colorectal cancer patients and controls in males by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We evaluated the clinical significance of sex hormones on colorectal cancer diagnosis with the area under the receiver operating characteristic curve (AUC). The role of genetic variants in hormone metabolic pathways in the colorectal cancer risk was assessed by a logistic regression model. The biological functions were detected by luciferase reporter assays and cell behavior experiments.

Results: We found that 2-methoxyestrone (2-MeO-E1) was highly expressed in cases (P = 3.48 × 10). The expression of 2-MeO-E1 in plasma showed improved accuracy for predicting colorectal cancer (AUC = 0.88). In the 2-MeO-E1 metabolic pathway, rs165599 in COMT was significantly associated with an increased risk of colorectal cancer (P = 0.009). Mechanistically, we found that the rs165599 G allele could decrease the binding ability of miR-22-3p to the COMT 3'-UTR. Furthermore, knockdown of COMT inhibited cell proliferation, induced cell apoptosis and arrested the cell cycle in the G1 phase.

Conclusion: This is the first study to show that 2-MeO-E1 and a genetic variant in COMT contribute to the susceptibility to colorectal cancer. These results shed light on the different incidence of colorectal cancer between the sexes.
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http://dx.doi.org/10.1016/j.envint.2020.105543DOI Listing
April 2020