Characteristics of the oral and gastric microbiome in patients with early-stage intramucosal esophageal squamous cell carcinoma.

BACKGROUND: Oral microbiome dysbacteriosis has been reported to be associated with the pathogenesis of advanced esophageal cancer. However, few studies investigated the potential role of oral and gastric microbiota in early-stage intramucosal esophageal squamous carcinoma (EIESC). METHOD: A total of 104 samples were collected from 31 patients with EIESC and 21 healthy controls. The compositions of oral and gastric microbiota were analyzed using 16 S rRNA V3-V4 amplicon sequencing. Linear discriminant analysis effect size (LEfSe) analysis was performed to assess taxonomic differences between groups. The correlation between oral microbiota and clinicopathological factors was evaluated using Spearman correlation analysis. Additionally, co-occurrence networks were established and random forest models were utilized to identify significant microbial biomarkers for distinguishing between the EIESC and control groups. RESULTS: A total of 292 oral genera and 223 species were identified in both EIESC and healthy controls. Six oral genera were remarkably enriched in EIESC groups, including the genera Porphyromonas, Shigella, Subdoligranulum, Leptotrichia, Paludibacter, and Odoribacter. LEfSe analysis identified genera Porphyromonas and Leptotrichia with LDA scores > 3. In the random forest model, Porphyromonas endodontalis ranked the top microbial biomarker to differentiate EIESC from controls. The elimination rate of Porphyromonas endodontalis from the oral cavity to the stomach was also dramatically decreased in the EIESC group than controls. In the microbial co-occurrence network, Porphyromonas endodontalis was positively correlated with Prevotella tannerae and Prevotella intermedia and was negatively correlated with Veillonella dispar. CONCLUSION: Our study potentially indicates that the dysbacteriosis of both the oral and gastric microbiome was associated with EIESC. Larger scale studies and experimental animal models are urgently needed to confirm the possible role of microbial dysbacteriosis in the pathogenesis of EIESC. (Chinese Clinical Trial Registry Center, ChiCTR2200063464, Registered 07 September 2022, https://www.chictr.org.cn/showproj.html?proj=178563).

Associations of arsenic exposure with liver injury in US adults: NHANES 2003-2018.

Arsenic is a natural element with complex toxicity. Long-term exposure to arsenic can cause a variety of health damage. In recent years, there are some studies on arsenic exposure and liver injury. But few of them tried to measure the quantitative relationship between arsenic exposure and indicators of liver injury in adult. Therefore, this study aimed to elucidate the relationship between them. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) in 2003-2018. Arsenic exposure was assessed using total urinary arsenic and dimethylarsenate acid (DMA). We selected alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total protein (TP), ALT/AST, total bilirubin (TBIL), and albumin (ALB) as markers of liver injury. Multiple linear regression was used to explore the relationship between urinary arsenic concentrations and these markers of liver function injury. In addition, six covariables (age, sex, smoker, alcohol user, BMI, diabetes) were further analyzed in subgroups. A total of 13,420 adults were included in the analysis. The multivariate linear regression analyses showed that urinary DMA was positively correlated with ALT (ß 0.135, 95%CI 0.090, 0.180, p < 0.001), AST (ß 0.053, 95%CI 0.014, 0.092, p < 0.01), ALT/AST (ß 0.052, 95%CI 0.030, 0.074, p < 0.001), TBIL (ß 0.061, 95%CI 0.034, 0.089, p < 0.001), and GGT (ß 0.178, 95%CI 0.110, 0.246, p < 0.001). Similar results were observed for total urinary arsenic, suggesting a positive association with AST (ß 0.048, 95%CI 0.016, 0.081, p < 0.01), ALT (ß 0.090, 95%CI 0.049, 0.132, p < 0.001), and TBIL (ß 0.062, 95%CI 0.037, 0.088, p < 0.001). In subgroup analysis, sex and smoker showed significant differences between subgroups. Our results demonstrate a positive association between urinary arsenic exposure and liver injury in adults. Sex and smokers may be related to arsenic pathogenicity.

Metagenomic analysis of the interaction between the gut microbiota and colorectal cancer: a paired-sample study based on the GMrepo database.

BACKGROUND: Previous evidence has shown that the gut microbiota plays a role in the development and progression of colorectal cancer (CRC). This study aimed to provide quantitative analysis and visualization of the interaction between the gut microbiota and CRC in order to establish a more precise microbiota panel for CRC diagnosis. METHOD: A paired-sample study was designed by retrieving original metagenomic data from the GMrepo database. The differences in the distribution of the gut microbiota between CRCs and controls were analysed at the species level. A co-occurrence network was established, and the microbial interactions with environmental factors were assessed. Random forest models were used to determine significant biomarkers for differentiating CRC and control samples. RESULTS: A total of 709 metagenomic samples from 6 projects were identified. After matching, 86 CRC patients and 86 matched healthy controls from six countries were enrolled. A total of 484 microbial species and 166 related genera were analysed. In addition to previously recognized associations between Fusobacterium nucleatum and species belonging to the genera Peptostreptococcus, Porphyromonas, and Prevotella and CRC, we found new associations with the novel species of Parvimonas micra and Collinsella tanakaei. In CRC patients, Bacteroides uniformis and Collinsella tanakaei were positively correlated with age, whereas Dorea longicatena, Adlercreutzia equolifaciens, and Eubacterium hallii had positive associations with body mass index (BMI). Finally, a random forest model was established by integrating different numbers of species with the highest model-building importance and lowest inner subcategory bias. The median value of the area under the receiver operating characteristic curve (AUC) was 0.812 in the training cohort and 0.790 in the validation set. CONCLUSIONS: Our study provides a novel bioinformatics approach for investigating the interaction between the gut microbiota and CRC using an online free database. The identification of key species and their associated genes should be further emphasized to determine the relative causality of microbial organisms in the development of CRC.

Establishment of a Preoperative Laboratory Panel to identify Lymph Node Metastasis in Superficial Esophageal Cancer.

Background and Aims: In superficial esophageal squamous cell carcinoma (SESCC), the lymph node status is considered as one of the essential factors to determine the primary treatment strategy. Nevertheless, current noninvasive staging methods before surgical intervention have limited accuracy. This study aimed to establish a simple and noninvasive serum-testing panel that facilitates the preoperative prediction of pathological nodal status in SESCC patients. Methods: Data for preoperative hematological parameters were retrospectively collected from 256 SESCC patients who underwent esophagectomy from December 2017 to May 2020. The random forest classification and decision tree algorithms were applied to identify the optimal combination of serum parameters for accurately identifying positive nodal metastasis. Results: Twelve candidate parameters were identified for statistical significance in predicting positive nodal metastasis. A multi-analyte panel was established by using a random forest classification method, incorporating four optimal parameters: Hematocrit (HCT), Activated Partial Thromboplastin Time (APTT), Retinol-Binding Proteins (RBP), and Mean Platelet Volume (MPV). A schematic decision tree was yielded from the above panel with an 89.1% accuracy of classification capability. Conclusions: This study established a simple laboratory panel in discerning the preoperative lymph nodal status of SESCC patients. With further validation, this panel may serve as a simple tool for clinicians to choose appropriate intervention (surgery versus endoscopic resection) for SESCC patients.

Alternative splicing of OsGS1;1 affects nitrogen-use efficiency, grain development, and amylose content in rice.

Excessive nitrogen fertilizer application is harmful to the environment and reduces the quality of cereal crops. Maintaining crop yields under low nitrogen (LN) conditions and improving quality are important goals for cereal crop breeding. Although the effects of nitrogen assimilation on crop nitrogen-use efficiency (NUE) have been intensively studied, natural variations of the key assimilation genes underlying grain development and quality are largely unclear. Here, we identified an NUE-associated gene, OsGS1;1, encoding glutamine synthase, through genome-wide association analysis, followed by validation experiments and functional analysis. Fifteen single-nucleotide polymorphisms in the OsGS1;1 region led to alternative splicing that generated two functional transcripts: OsGS1;1a and OsGS1;1b. The elite haplotype of OsGS1;1 showed high OsGS1;1b activity, which improved NUE, affected grain development, and reduced amylose content. The results show that OsGS1;1, which is induced under LN conditions, affects grain formation by regulating sugar metabolism and may provide a new avenue for the breeding of high-yield and high-quality rice (Oryza sativa).

Enhanced OsNLP4-OsNiR cascade confers nitrogen use efficiency by promoting tiller number in rice.

Increased use of nitrogen fertilizers has deleterious impact on the environment. Increase in yield potential at low nitrogen supply is regarded as a cereal breeding goal for future agricultural sustainability. Although natural variations of nitrogen transporters have been investigated, key genes associated with assimilation remain largely unexplored for nitrogen use efficiency (NUE) enhancement. Here, we identified a NIN-like protein NLP4 associated with NUE through a GWAS in rice. We found that OsNLP4 transactivated OsNiR encoding nitrite reductase that was critical in nitrogen assimilation in rice. We further constructed quadrupling NREs (Nitrate-responsive cis-elements) in the promoter of OsNiR (p4xNRE:OsNiR) and enhanced nitrogen assimilation significantly. We demonstrated that OsNLP4-OsNiR increased tiller number and yield through enhancing nitrogen assimilation and NUE. Our discovery highlights the genetic modulation of OsNLP4-OsNiR signalling cascade as a strategy for high NUE and yield breeding in rice.

Heterosis-associated genes confer high yield in super hybrid rice.

KEY MESSAGE: Heterosis QTLs, including qSS7 and qHD8, with dominance effects were identified through GBS and large-scale phenotyping of CSSLs and hybrid F1 populations in a paddy field. Heterosis has contributed immensely to agricultural production, but its genetic basis is unclear. We evaluated dominance effects by creating two hybrid populations: a B-homo set with a homozygous background and heterozygous chromosomal segments and a B-heter set with a heterozygous background and homozygous segments. This was achieved by crossing a set of 156 backcrossed-derived chromosome segment substitution lines (CSSLs) with their recurrent parent (9311), the male parent of the first super-high-yield hybrid Liangyoupei9 (LYP9), and with the female parent (PA64s) of the hybrid. The CSSLs were subjected to a genotyping-by-sequencing analysis to develop a genetic map of segments introduced from the PA64s. We evaluated the heterotic effects on eight yield-related traits in the hybrid variety and F1 populations in large-scale field experiments over 2 years. Using a linkage map consisting of high-density SNPs, we identified heterosis-associated genes in LYP9. Five candidate genes contributed to the high yield of LYP9, with qSS7 and qHD8 repeatedly detected in both B-hybrid populations. The heterozygous segments harboring qSS7 and qHD8 showed dominance effects that contributed to the heterosis of yield components in the hybrid rice variety Liangyoupei9.

Comparative analysis of codon usage patterns in chloroplast genomes of six Euphorbiaceae species.

Euphorbiaceae plants are important as suppliers of biodiesel. In the current study, the codon usage patterns and sources of variance in chloroplast genome sequences of six different Euphorbiaceae plant species have been systematically analyzed. Our results revealed that the chloroplast genomes of six Euphorbiaceae plant species were biased towards A/T bases and A/T-ending codons, followed by detection of 17 identical high-frequency codons including GCT, TGT, GAT, GAA, TTT, GGA, CAT, AAA, TTA, AAT, CCT, CAA, AGA, TCT, ACT, TAT and TAA. It was found that mutation pressure was a minor factor affecting the variation of codon usage, however, natural selection played a significant role. Comparative analysis of codon usage frequencies of six Euphorbiaceae plant species with four model organisms reflected that Arabidopsis thaliana, Populus trichocarpa, and Saccharomyces cerevisiae should be considered as suitable exogenous expression receptor systems for chloroplast genes of six Euphorbiaceae plant species. Furthermore, it is optimal to choose Saccharomyces cerevisiae as the exogenous expression receptor. The outcome of the present study might provide important reference information for further understanding the codon usage patterns of chloroplast genomes in other plant species.

Genome-wide associated study identifies NAC42-activated nitrate transporter conferring high nitrogen use efficiency in rice.

Over-application of nitrogen fertilizer in fields has had a negative impact on both environment and human health. Domesticated rice varieties with high nitrogen use efficiency (NUE) reduce fertilizer for sustainable agriculture. Here, we perform genome-wide association analysis of a diverse rice population displaying extreme nitrogen-related phenotypes over three successive years in the field, and identify an elite haplotype of nitrate transporter OsNPF6.1HapB that enhances nitrate uptake and confers high NUE by increasing yield under low nitrogen supply. OsNPF6.1HapB differs in both the protein and promoter element with natural variations, which are differentially trans-activated by OsNAC42, a NUE-related transcription factor. The rare natural allele OsNPF6.1HapB, derived from variation in wild rice and selected for enhancing both NUE and yield, has been lost in 90.3% of rice varieties due to the increased application of fertilizer. Our discovery highlights this NAC42-NPF6.1 signaling cascade as a strategy for high NUE and yield breeding in rice.