Positive associations fuel soil biodiversity and ecological networks worldwide.

Microbial interactions are key to maintaining soil biodiversity. However, whether negative or positive associations govern the soil microbial system at a global scale remains virtually unknown, limiting our understanding of how microbes interact to support soil biodiversity and functions. Here, we explored ecological networks among multitrophic soil organisms involving bacteria, protists, fungi, and invertebrates in a global soil survey across 20 regions of the planet and found that positive associations among both pairs and triads of soil taxa governed global soil microbial networks. We further revealed that soil networks with greater levels of positive associations supported larger soil biodiversity and resulted in lower network fragility to withstand potential perturbations of species losses. Our study provides unique evidence of the widespread positive associations between soil organisms and their crucial role in maintaining the multitrophic structure of soil biodiversity worldwide.

Genetic variants in hypoxia-inducible factor pathway are associated with colorectal cancer risk and immune infiltration.

Hypoxia-inducible factor (HIF) pathway genes influence tumorigenesis and immune status. However, the associations between genetic variants in hypoxia-related genes and colorectal cancer risk and the immune status of hypoxia-associated genes in colorectal cancer have not been systematically characterized. The associations between genetic variants and colorectal cancer risk were evaluated in Chinese, Japanese and European populations using logistic regression analysis. The relationships between target genes and tumour immune infiltration were predicted by Tumour Immune Estimation Resource (TIMER). We found that rs34533650 in EPAS1 was associated with colorectal cancer risk (OR = 1.43, 95% CI = 1.20-1.70, P(FDR) = 8.35 × 10-4 ), and this finding was validated in two independent populations (Japanese: OR = 1.07, 95% CI = 1.01-1.15, p = 3.38 × 10-2 ; European: OR = 1.11, 95% CI = 1.03-1.19, p = 6.04 × 10-3 ). EPAS1-associated genes were enriched in immune-related pathways. In addition, we found that EPAS1 copy number variation (CNV) was associated with the degree of infiltration of immune cells and observed correlations between EPAS1 expression and immune cell infiltration levels in colorectal cancer. These results highlight that genetic variants of hypoxia-related genes play roles in colorectal cancer risk and provide new insight that EPAS1 might be a promising predictor of colorectal cancer susceptibility and immune status.

AKR1C2 genetic variants mediate tobacco carcinogens metabolism involving bladder cancer susceptibility.

Tobacco carcinogens metabolism-related genes (TCMGs) could generate reactive metabolites of tobacco carcinogens, which subsequently contributed to multiple diseases. However, the association between genetic variants in TCMGs and bladder cancer susceptibility remains unclear. In this study, we derived TCMGs from metabolic pathways of polycyclic aromatic hydrocarbons and tobacco-specific nitrosamines, and then explored genetic associations between TCMGs and bladder cancer risk in two populations: a Chinese population of 580 cases and 1101 controls, and a European population of 5930 cases and 5468 controls, along with interaction and joint analyses. Expression patterns of TCMGs were sourced from Nanjing Bladder Cancer (NJBC) study and publicly available datasets. Among 43 TCMGs, we observed that rs7087341 T > A in AKR1C2 was associated with a reduced risk of bladder cancer in the Chinese population [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.72-0.97, P = 1.86 × 10-2]. Notably, AKR1C2 rs7087341 showed an interaction effect with cigarette smoking on bladder cancer risk (Pinteraction = 5.04 × 10-3), with smokers carrying the T allele increasing the risk up to an OR of 3.96 (Ptrend < 0.001). Genetically, rs7087341 showed an allele-specific transcriptional regulation as located at DNA-sensitive regions of AKR1C2 highlighted by histone markers. Mechanistically, rs7087341 A allele decreased AKR1C2 expression, which was highly expressed in bladder tumors that enhanced metabolism of tobacco carcinogens, and thereby increased DNA adducts and reactive oxygen species formation during bladder tumorigenesis. These findings provided new insights into the genetic mechanisms underlying bladder cancer.

Protein Phosphatase 2A Activation Via ApoER2 in Trophoblasts Drives Preeclampsia in a Mouse Model of the Antiphospholipid Syndrome.

[Figure: see text].

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N6-Methyladenosine Modification of ATP13A3.

Element contamination, including that from heavy metals, is associated with gastrointestinal tumorigenesis, but the effects and mechanisms of crucial element exposure associated with colorectal cancer remain unclear. We profiled 56 elements by ICP-MS and used logistic regression, LASSO, BKMR, and GAM to identify colorectal cancer-relevant elements. A series of biochemical experiments were performed to demonstrate the cytotoxicity and the mechanisms of malignant transformation after metal exposure. Using an elementomics approach, we first found that the metal thallium (Tl) was positively correlated with many toxic metals and was associated with a significantly increased risk of colorectal cancer. Acute exposure to Tl induced cytotoxicity and cell death by accelerating the generation of reactive oxygen species and DNA damage. Chronic exposure to Tl led to the inhibition of cell death and thereby induced the malignant transformation of normal colon cells and xenograft tumor formation in nude mice. Furthermore, we describe the first identification of a significant metal quantitative trait locus for the novel colorectal cancer susceptibility locus rs1511625 near ATP13A3. Mechanistically, Tl increased the level of aberrant N6-methyladenosine (m6A) modification of ATP13A3 via the METLL3/METTL14/ALKBH5-ATP13A3 axis to promote colorectal tumorigenesis. This study provides a basis for the development of public health strategies for reducing metal exposure among populations at high risk for colorectal cancer.

Soil edaphic factors and climate seasonality explain the turnover of methanotrophic communities in riparian wetlands.

Aerobic CH4-oxidizing bacteria (methanotrophs) represent a biological model system for the removal of atmospheric CH4, which is sensitive to the dynamics of water tables. However, little attention has been given to the turnover of methanotrophic communities across wet and dry periods in riparian wetlands. Here, by sequencing the pmoA gene, we investigated the turnover of soil methanotrophic communities across wet and dry periods in typical riparian wetlands that experience intensive agricultural practices. The results demonstrated that the methanotrophic abundance and diversity were significantly higher in the wet period than in the dry period, probably owing to the climatic seasonal succession and associated variation in soil edaphic factors. The co-occurrence patterns of the interspecies association analysis demonstrated that the key ecological clusters (i.e., Mod#1, Mod#2, Mod#4, Mod#5) showed contrasting correlations with soil edaphic properties between wet and dry periods. The linear regression slope of the relationships between the relative abundance of Mod#1 and the carbon to nitrogen ratio was higher in the wet period than in the dry period, whereas the linear regression slope of the relationships between the relative abundance of Mod#2 and soil nitrogen content (i.e., dissolved organic nitrogen, nitrate, and total nitrogen) was higher in the dry period than in the wet period. Moreover, Stegen's null model combined with phylogenetic group-based assembly analysis demonstrated that the methanotrophic community exhibited a higher proportion of drift (55.0%) and a lower contribution of dispersal limitation (24.5%) in the wet period than in the dry period (43.8% and 35.7%, respectively). Overall, these findings demonstrate that the turnover of methanotrophic communities across wet and dry periods were soil edaphic factors and climate dependent.

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

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.

Exosomal circCLIP1 regulates PM2.5-induced airway obstruction via targeting SEPT10 in vitro.

Fine particulate matter (PM2.5) exposure correlates with airway obstruction, but the mechanism remains to be fully elucidated. We aim to investigate the role of exosomal circular RNAs (circRNAs)-mediated communication between airway epithelial cells and airway smooth muscle cells in PM2.5-induced airway obstruction. RNA sequencing revealed that acute PM2.5 exposure altered the expression profiles of 2904 exosomal circRNAs. Among them, exosomal hsa_circ_0029069 (spliced from CLIP1, thus termed circCLIP1 hereafter) with a loop structure was upregulated by PM2.5 exposure and mainly encapsulated in exosomes. Then, the biological functions and the underlying mechanisms were explored by Western blot, RNA immunoprecipitation and RNA pull-down, etc. Phenotypically, exosomal circCLIP1 entered recipient cells, inducing mucus secretion in recipient HBE cells and contractility of sensitive HBSMCs. Mechanistically, circCLIP1 was upregulated by METTL3-mediated N6-methyladenine (m6A) modification in PM2.5-treated producer HBE cells and exosomes, then enhancing the expression of SEPT10 in recipient HBE cells and sensitive HBSMCs. Our study revealed that exosomal circCLIP1 played a critical role in PM2.5-induced airway obstruction and provided a new potential biomarker for the assessment of PM2.5-related adverse effects.

Exosomal circLPAR1 functions in colorectal cancer diagnosis and tumorigenesis through suppressing BRD4 via METTL3-eIF3h interaction.

BACKGROUND: Exosomes have emerged as vital biomarkers of multiple cancers and contain abundant circular RNAs (circRNAs). However, the potential for exosomal circRNAs to be used in diagnostics and their molecular mechanism of action in colorectal cancer (CRC) remain unclear. METHODS: CRC-specific exosomal circRNAs were identified by RNA sequencing, exoRBase database and a tissue microarray. The diagnostic performance of plasma exosomal circRNAs was evaluated among cancer-free controls, precancer individuals, CRC patients, and patients with other types of cancer. The corresponding biological functions were mainly assessed using circRNA pull-down, proteomic analysis, and RNA immunoprecipitation assay underlying cellular and mouse models. RESULTS: CircLPAR1 was encapsulated in exosomes with high stability and detectability, and its expression in plasma exosomes was remarkably decreased during CRC development but recovered after surgery. Exosomal circLPAR1 showed cancer specificity in CRC diagnosis and increased the diagnostic performance to an area under the receiver operating characteristic curve of 0.875, as determined by analysing its performance in combination with common clinical biomarkers CEA and CA19-9. Additionally, circLPAR1 was downregulated in CRC tissues and was associated with overall survival. Mechanistically, exosomal circLPAR1 was internalized by CRC cells, and it suppressed tumor growth, likely because exosomal circLPAR1 directly bound with eIF3h specifically suppressed the METTL3-eIF3h interaction, decreasing the translation of oncogene BRD4. CONCLUSIONS: This comprehensive study highlights plasma exosomal circLPAR1 as a promising predictor in CRC diagnosis and describes its biological regulation of colorectal tumorigenesis. This study provides a new perspective on early diagnosis in the clinic and pathogenesis in disease development.

CoSMeD: a user-friendly web server to estimate 5-year survival probability of left-sided and right-sided colorectal cancer patients using molecular data.

SUMMARY: Colorectal cancer is a heterogeneous disease with diverse prognoses between left-sided and right-sided patients; therefore, it is necessary to precisely evaluate the survival probability of side-specific colorectal cancer patients. Here, we collected multi-omics data from The Cancer Genome Atlas program, including gene expression, DNA methylation and microRNA expression. Specificity measure and robust likelihood-based survival analysis were used to identify 6 left-sided and 28 right-sided prognostic biomarkers. Compared to the performance of clinical prognostic models, the addition of these biomarkers could significantly improve the discriminatory ability and calibration in predicting side-specific 5-year survival for colorectal cancer. Additional dataset derived from Gene Expression Omnibus was used to validate the prognostic value of side-specific genes. Finally, we constructed colorectal cancer side-specific molecular database (CoSMeD), a user-friendly interface for estimating side-specific colorectal cancer 5-year survival probability, which can lay the basis for personalized management of left-sided and right-sided colorectal cancer patients. AVAILABILITY AND IMPLEMENTATION: CoSMeD is freely available at https://mulongdu.shinyapps.io/cosmed. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Continental-scale plant invasions reshuffle the soil microbiome of blue carbon ecosystems.

Theory and experiments support that plant invasions largely impact aboveground biodiversity and function. Yet, much less is known on the influence of plant invasions on the structure and function of the soil microbiome of coastal wetlands, one of the largest major reservoirs of biodiversity and carbon on Earth. We studied the continental-scale invasion of Spartina alterniflora across 2451 km of Chinese coastlines as our model-system and found that S. alterniflora invasion can largely influence the soil microbiome (across six depths from 0 to 100 cm), compared with the most common microhabitat found before invasion (mudflats, Mud). In detail, S. alterniflora invasion was not only positively associated with bacterial richness but also resulted in important biotic homogenization of bacterial communities, suggesting that plant invasion can lead to important continental scale trade-offs in the soil microbiome. We found that plant invasion changed the community composition of soil bacterial communities across the soil profile. Moreover, the bacterial communities associated with S. alterniflora invasions where less responsive to climatic changes than those in native Mud microhabitats, suggesting that these new microbial communities might become more dominant under climate change. Plant invasion also resulted in important reductions in the complexity and stability of microbial networks, decoupling the associations between microbes and carbon pools. Taken together, our results indicated that plant invasions can largely influence the microbiome of coastal wetlands at the scale of China, representing the first continental-scale example on how plant invasions can reshuffle the soil microbiome, with consequences for the myriad of functions that they support.

Chlorinated Organophosphate Flame Retardants Impair the Lung Function via the IL-6/JAK/STAT Signaling Pathway.

Toxicological studies have revealed the adverse impacts of organophosphate flame retardants (OPFRs) on the respiratory system, while there is a lack of epidemiological evidence, and information for risk assessment remains insufficient. Herein, we investigated the associations of urinary metabolites of OPFRs with the lung function in 987 adults participating in the U.S. National Health and Nutrition Examination Survey 2011-2012. The elevation of three primary metabolites of chlorinated OPFRs [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(2-chloroethyl) phosphate (BCEP), and bis(1-chloro-2-propyl) phosphate (BCIPP)] was related to pulmonary dysfunction in a sample-weighted regression model. Each one-unit increase in the log-transformed levels of BDCIPP and BCEP was related to 91.52 and 79.34 mL reductions in the forced vital capacity (FVC). Each one-unit elevation in BCIPP was correlated with 130.86, 153.56, 302.26, and 148.24 mL reductions in forced expiratory volume 1st second (FEV1), FVC, peak expiratory flow rate (PEF), and forced expiratory flow at 25-75% of FVC (FEF25-75%), respectively. Then, an adverse outcome pathway (AOP) framework was constructed using the Comparative Toxicogenomics Database, the Toxicity Forecaster, and the GeneCards database. Based on the weight of the evidence, BDCIPP, BCEP, BCIPP, and their parent compounds (TDCIPP, TCEP, and TCIPP) may affect the IL-6/Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, induce airway remodeling, and impair the lung function. Additionally, tobacco smoke exposure may modify the effects of BDCIPP on the lung function (Pint < 0.05) and affect the IL-6-mediated AOP. These results suggested that chlorinated OPFRs were associated with pulmonary dysfunction via the IL-6/JAK/STAT pathway.

Genetic variants in choline metabolism pathway are associated with the risk of bladder cancer in the Chinese population.

Choline metabolism alteration is considered as a metabolic hallmark in cancer, reflecting the complex interactions between carcinogenic signaling pathways and cancer metabolism, but little is known about whether genetic variants in the metabolism pathway contribute to the susceptibility of bladder cancer. Herein, a case-control study comprising 580 patients and 1,101 controls was carried out to analyze the association of bladder cancer with genetic variants on candidate genes involved in the choline metabolism pathway using unconditional logistic regression. Gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were applied for differential gene expression analysis. Cox regression was also applied to estimate the role of candidate genes on bladder cancer prognosis. Our results demonstrated that C allele of rs6810830 in ENPP6 was a significant protective allele of bladder cancer, compared to the T allele [Odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.64-0.86, P = 7.14 × 10-5 in additive model]. Besides, we also found that the expression of ENPP6 remarkably decreased in bladder tumors compared with normal tissues. Moreover, high expression of ENPP6 was associated with worse overall survival (OS) in bladder cancer patients [hazard ratio (HR) with their 95% CI 1.39 (1.02-1.90), P = 0.039]. In conclusion, our results suggested that SNP rs6810830 (T > C) in ENPP6 might be a potential susceptibility loci for bladder cancer, and these findings provided novel insights into the underlying mechanism of choline metabolism in cancers.

Evaluation of genetic variants in nucleosome remodeling and deacetylase (NuRD) complex subunits encoding genes and gastric cancer susceptibility.

Epigenetic complex NuRD (nucleosome remodeling and deacetylase) engages in a range of basic cellular processes, including chromatin modification. Changes in the activity of NuRD complex can influence gastric cancer progression. Multivariate logistic regression analyses were used to estimate the association between single-nucleotide polymorphisms (SNPs) and gastric cancer risk. Expression quantitative trait loci (eQTL) analysis was used to analyze the relationship between the genotypes and gene expression levels using data from the genotype tissue expression project (GTEx). Gene expression was calculated using databases from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO). Kaplan-Meier plotter was used to evaluate the association between gene expression and survival. SNP rs11064275 T allele in CHD4, rs892022 A allele and rs2033481 A allele in GATAD2A were found to contribute to the decreased risk of gastric cancer. The increase in the number of favorable alleles of these three SNPs was associated with a lower risk of gastric cancer. rs2033481 and rs892022 were substantially correlated with GATAD2A mRNA expression levels. Meanwhile, we detected that the CHD4 and GATAD2A mRNA expression was increased in gastric cancer tissues compared with the adjacent normal tissues. Furthermore, we found that patients with higher CHD4 or GATAD2A mRNA expression level had more advantageous overall survival. Our findings indicated that genetic variants in NuRD complex subunits encoding genes may be promising predictors of gastric cancer risk.

Functional variants of RPS6KB1 and PIK3R1 in the autophagy pathway genes and risk of bladder cancer.

Autophagy plays a critical role in cancer, since it can either suppress tumorigenesis by inhibiting cancer cell survival, or facilitate tumorigenesis by promoting cancer cell proliferation and tumor growth. However, the role of genetic variants of autophagy-regulated key genes for bladder cancer risk remained unclear. Here, we aimed to explore the association of bladder cancer with genetic variants on genes involved in autophagy pathway. Gene-based analysis was performed with multi-marker analysis of genomic annotation (MAGMA) in 580 bladder cancer cases and 1101 controls. The logistic regression model was used to calculate the SNP effects on bladder cancer susceptibility. Expression quantitative trait loci (eQTL) analysis was conducted by the genotype-tissue expression (GTEx) project. Gene expression was evaluated based on the Cancer Genome Atlas (TCGA) database. Three potentially functional SNPs RPS6KB1 rs1292038, PIK3R1 rs34303, and rs56352616 were demonstrated to be associated with risk of bladder cancer (OR = 0.71, 95% CI = 0.61-0.82, P = 7.88 × 10-6 for rs1292038; OR = 1.25, 95% CI = 1.09-1.45, P = 2.11 × 10-3 for rs34303; OR = 0.74, 95% CI = 0.62-0.90, P = 2.47 × 10-3 for rs56352616). An increasing number of risk genotypes of these three SNPs were associated with a higher risk of developing bladder cancer. Besides, rs1292038 exhibited an eQTL effect for RPS6KB1 in whole blood (P = 3.90 × 10-7). Furthermore, the higher expression of RPS6KB1 and lower expression of PIK3R1 were both significantly associated with bladder cancer risk. Our findings indicated that genetic variants in autophagy pathway genes RPS6KB1 and PIK3R1 confer bladder cancer susceptibility.

Distribution and co-occurrence patterns of antibiotic resistance genes in black soils in Northeast China.

Black soils (Mollisols) are among the most important soil resources for crop production and food security. In China, they are mainly distributed in the northeastern region. To investigate soil antibiotic resistance distribution patterns and monitor soil quality, we randomly chose nine corn fields in Northeast China and analyzed the antibiotic resistance gene (ARG) distribution and co-occurrence patterns on the basis of high-throughput approaches and network analyses. High genetic diversity (136 unique genes) and low ARG abundances (10-5-10-2 copies/16S rRNA gene copy) were detected, with relatively few interactions among ARGs. Type I integron genes were prevalent in the soil and were positively correlated with ARGs, which may increase the risk of ARG transmission. Most ARGs were strongly associated with microorganisms. Moreover, several ARGs were significantly correlated with antibiotics, nutrients, and metal elements. The generation and dissemination of ARGs, which were most likely mediated by mobile genetic elements (MGEs) and bacteria, were affected by environmental conditions. These results provide insights into the widespread co-occurrence patterns in soil resistomes.

Increasing Inundation Frequencies Enhance the Stochastic Process and Network Complexity of the Soil Archaeal Community in Coastal Wetlands.

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. In this study, we established an in situ mesocosm with an inundation frequency gradient to investigate the response of soil archaeal community toward increasing inundation frequencies in monocultures of Spartina alterniflora and a mangrove species, Kandelia obovata 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 S. alterniflora soil displayed lower niche overlap and higher stochasticity than in K. obovata 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.IMPORTANCE Coastal wetlands, subjected to regular disturbances by periodic tides, 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 aimed at unraveling 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.

Differential Responses of Arbuscular Mycorrhizal Fungal Communities to Long-Term Fertilization in the Wheat Rhizosphere and Root Endosphere.

Arbuscular mycorrhizal fungi (AMF) provide essential nutrients to crops and are critically impacted by fertilization in agricultural ecosystems. Understanding shifts in AMF communities in and around crop roots under different fertilization regimes can provide important lessons for improving agricultural production and sustainability. Here, we compared the responses of AMF communities in the rhizosphere (RS) and root endosphere (ES) of wheat (Triticum aestivum) to different fertilization treatments, nonfertilization (control), mineral fertilization only (NPK), mineral fertilization plus wheat straw (NPKS), and mineral fertilization plus cow manure (NPKM). We employed high-throughput amplicon sequencing and investigated the diversity, community composition, and network structure of AMF communities to assess their responses to fertilization. Our results elucidated that AMF communities in the RS and ES respond differently to fertilization schemes. Long-term NPK application decreased the RS AMF alpha diversity significantly, whereas additional organic amendments (straw or manure) had no effect. In contrast, NPK fertilization increased the ES AMF alpha diversity significantly, while additional organic amendments decreased it significantly. The effect of different fertilization schemes on AMF network complexity in the RS and ES were similar to their effects on alpha diversity. Changes to AMF communities in the RS and ES correlated mainly with the pH and phosphorus level of the rhizosphere soil under long-term inorganic and organic fertilization regimes. We suggest that the AMF community in the roots should be given more consideration when studying the effects of fertilization regimes on AMF in agroecosystems. IMPORTANCE Arbuscular mycorrhizal fungi are an integral component of rhizospheres, bridging the soil and plant systems and are highly sensitive to fertilization. However, surprisingly little is known about how the response differs between the roots and the surrounding soil. Decreasing arbuscular mycorrhizal fungal diversity under fertilization has been reported, implying a potential reduction in the mutualism between plants and arbuscular mycorrhizal fungi. However, we found opposing responses to long-term fertilization managements of arbuscular mycorrhizal fungi in the wheat roots and rhizosphere soil. These results suggested that changes in the arbuscular mycorrhizal fungal community in soils do not reflect those in the roots, highlighting that the root arbuscular mycorrhizal fungal community is pertinent to understand arbuscular mycorrhizal fungi and their crop hosts' responses to anthropogenic influences.

Genetic variants in m6A regulators are associated with gastric cancer risk.

N6-methyladenosine (m6A) 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 m6A 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 × 10-3). This finding was repeated in an independent Nanjing population (OR = 0.76, 95% CI: 0.59-0.98, P = 3.45 × 10-2). 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 × 10-4). 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 × 10-3). For the first time, our findings suggested the importance of genetic variants in m6A regulators in GC and indicated that IGF2BP1 plays a crucial role in GC. Genetic variants in m6A modification genes may be used for GC risk prediction.

Genetic variations in the CTLA-4 immune checkpoint pathway are associated with colon cancer risk, prognosis, and immune infiltration via regulation of IQCB1 expression.

The programmed cell death-1 (PD-1)/cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint pathways serve as targets of immunotherapy for colorectal cancer. However, the associations between genetic variations in these pathways and colorectal cancer risk, prognosis, and immune status remain unclear. The associations between single-nucleotide polymorphisms (SNPs) and colorectal cancer risk and survival were evaluated in a case-control study comprising 1150 cases and 1342 controls along with 287 cases with overall survival information. We found that individuals with the A allele of B7-2 rs2681416 in CTLA-4 immune checkpoint pathway had a significantly increased risk of colorectal cancer [odds ratio (OR) = 1.37, P = 3.17 × 10-4] than those with G allele under the dominant model, which had a predominant site-specific effect in colon cancer (OR = 1.55, P = 3.11 × 10-5). In addition, rs2681416 significantly decreased the overall survival time of patients with colon cancer [hazard ratio (HR) = 1.96, P = 1.10 × 10-2], but not of patients with rectal cancer (P = 0.271). Moreover, rs2681416 had an expression quantitative trait locus effect on the B7-2 flanking gene IQCB1 in colon tissues, which contributed to colon cancer risk by regulating genome organization and influenced the expression of IQCB1 in an allele-specific manner. IQCB1 expression was upregulated in colorectal cancer tissues compared with normal tissues, accounting for various critical carcinogenic states in colon cancer and promoting immune infiltration of Th17 cells in the tumor microenvironment. Our study highlights the important roles of genetic variations in immune checkpoint pathways and provides new insight into potential site-specific independent biomarkers for colorectal cancer susceptibility, prognosis, and tumor immune status.