A novel strategy for detoxification of deoxynivalenol via modification of both toxic groups.

Deoxynivalenol (DON) is the most abundant mycotoxin in cereal crops and derived foods and is of great concern in agriculture. Bioremediation strategies have long been sought to minimize the impact of mycotoxin contamination, but few direct and effective enzyme-catalyzed detoxification methods are currently available. In this study, we established a multi-enzymatic cascade reaction and successfully achieved detoxification at double sites: glutathionylation for the C-12,13 epoxide group and epimerization for the C-3 hydroxyl group. This yielded novel derivatives of DON, 3-epi-DON-13-glutathione (3-epi-DON-13-GSH) as well as its by-product, 3-keto-DON-13-GSH, for which precise structures were validated via liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Both cell viability and DNA synthesis assays demonstrated dramatically decreased cytotoxicity of the double-site modified product 3-epi-DON-13-GSH. These findings provide a promising and urgently needed novel method for addressing the problem of DON contamination in agricultural and industrial settings.

Fhb7-GST catalyzed glutathionylation effectively detoxifies the trichothecene family.

Trichothecene (TCN) contamination in food and feed is a serious challenge due to the negative health and economic impacts. Here, we confirmed that the glutathione S-transferase (GST) Fhb7-GST could broadly catalyze type A, type B and type D TCNs into glutathione epoxide adducts (TCN-13-GSHs). To evaluate the toxicity of TCN-13-GSH adducts, we performed cell proliferation assays in vitro, which demonstrated decreased cytotoxicity of the adducts. Moreover, in vivo assays (repeated-dose treatment in mice) confirmed that TCN-13-GSH adducts were dramatically less toxic than the corresponding TCNs. To establish whether TCN-13-GSH was metabolized back to free toxin during digestion, single-dose metabolic tests were performed in rats; DON-13-GSH was not hydrolyzed in vivo, but rather was quickly metabolized to another low-toxicity compound, DON-13-N-acetylcysteine. These results demonstrate the promise of Fhb7-GST as a candidate of detoxification enzyme potentially applied in TCN-contaminated agricultural samples, minimizing the detrimental effects of the mycotoxin.

Correlation between the salivary microbiology and H2 S concentration of the oral cavity.

BACKGROUND: Hydrogen sulfide (H2 S) is the most important compound causing oral malodor, and its concentration is thought to be closely correlated with oral microorganism activity. Therefore, clarifying the correlation between oral microbes and metabolites is important. METHODS: This study tested with 16S rRNA gene amplicon and shotgun metagenomic sequencing of oral microorganisms and oral malodor tests. RESULTS: There were different of the microbial taxa between the low and high H2 S groups. And in the high H2 S group, most of the enriched taxa were genera which abundance was correlated with H2 S concentration. Fusobacterium periodonticum and Prevotella nanceiensis were significantly different in coverage breadth and depth and in LPS biosynthesis contributions between the two groups. The contribution of F. periodonticum to sulfur metabolism was significantly different between the two groups, and the relative F. periodonticum abundance was higher in the high H2 S group. CONCLUSIONS: The H2 S content is significantly associated with the oral cavity microorganism composition and abundance. Most microorganisms enriched in people with high H2 S levels are associated with oral diseases such as caries and periodontal diseases.

Gut metagenomic characteristics of ADHD reveal low Bacteroides ovatus-associated host cognitive impairment.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous psychiatric disorder that can have three phenotypical presentations: inattentive (I-ADHD), hyperactive-impulsive (HI-ADHD), and combined (C-ADHD). Environmental factors correlated with the gut microbiota community have been implicated in the development of ADHD. However, whether different ADHD symptomatic presentations are associated with distinct microbiota compositions and whether patients could benefit from the correction of aberrant bacterial colonization are still largely unclear. We carried out metagenomic shotgun analysis with 207 human fecal samples to characterize the gut microbial profiles of patients with ADHD grouped according to their phenotypical presentation. Then, we transplanted the candidate low-abundance bacteria identified in patient subgroups into ADHD rats and evaluated ADHD-associated behaviors and neuronal activation in these rats. Patients with C-ADHD had a different gut microbial composition from that of healthy controls (HCs) (p = .02), but not from that of I-ADHD patients. Eight species became progressively attenuated or enriched when comparing the compositions of HCs to those of I-ADHD and C-ADHD; in particular, the abundance of Bacteroides ovatus was depleted in patients with C-ADHD. In turn, Bacteroides ovatus supplementation ameliorated spatial working memory deficits and reversed θ electroencephalogram rhythm alterations in ADHD rats. In addition, Bacteroides ovatus induced enhanced neuronal activation in the hippocampal CA1 subregion. These findings indicate that gut microbial characteristics that are unique to patients with C-ADHD may be masked when considering a more heterogeneous group of patients. We link the gut microbiota to brain function in an ADHD animal model, suggesting the relevance of testing a potential bacteria-based intervention for some aspects of ADHD.

Wheat genomic study for genetic improvement of traits in China.

Bread wheat (Triticum aestivum L.) is a major crop that feeds 40% of the world's population. Over the past several decades, advances in genomics have led to tremendous achievements in understanding the origin and domestication of wheat, and the genetic basis of agronomically important traits, which promote the breeding of elite varieties. In this review, we focus on progress that has been made in genomic research and genetic improvement of traits such as grain yield, end-use traits, flowering regulation, nutrient use efficiency, and biotic and abiotic stress responses, and various breeding strategies that contributed mainly by Chinese scientists. Functional genomic research in wheat is entering a new era with the availability of multiple reference wheat genome assemblies and the development of cutting-edge technologies such as precise genome editing tools, high-throughput phenotyping platforms, sequencing-based cloning strategies, high-efficiency genetic transformation systems, and speed-breeding facilities. These insights will further extend our understanding of the molecular mechanisms and regulatory networks underlying agronomic traits and facilitate the breeding process, ultimately contributing to more sustainable agriculture in China and throughout the world.

Wheat-Thinopyrum Substitution Lines Imprint Compensation Both From Recipients and Donors.

Even frequently used in wheat breeding, we still have an insufficient understanding of the biology of the products via distant hybridization. In this study, a transcriptomic analysis was performed for six Triticum aestivum-Thinopyrum elongatum substitution lines in comparison with the host plants. All the six disomic substitution lines showed much stronger "transcriptomic-shock" occurred on alien genomes with 57.43-69.22% genes changed expression level but less on the recipient genome (2.19-8.97%). Genome-wide suppression of alien genes along chromosomes was observed with a high proportion of downregulated genes (39.69-48.21%). Oppositely, the wheat recipient showed genome-wide compensation with more upregulated genes, occurring on all chromosomes but not limited to the homeologous groups. Moreover, strong co-upregulation of the orthologs between wheat and Thinopyrum sub-genomes was enriched in photosynthesis with predicted chloroplastic localization, which indicates that the compensation happened not only on wheat host genomes but also on alien genomes.

Genome-wide identification, characteristics and expression of the prolamin genes in Thinopyrum elongatum.

BACKGROUND: Prolamins, unique to Gramineae (grasses), play a key role in the human diet. Thinopyrum elongatum (syn. Agropyron elongatum or Lophopyrum elongatum), a grass of the Triticeae family with a diploid E genome (2n = 2x = 14), is genetically well-characterized, but little is known about its prolamin genes and the relationships with homologous loci in the Triticeae species. RESULTS: In this study, a total of 19 α-gliadin, 9 γ-gliadin, 19 ω-gliadin, 2 high-molecular-weight glutenin subunit (HMW-GS), and 5 low-molecular-weight glutenin subunit (LMW-GS) genes were identified in the Th. elongatum genome. Micro-synteny and phylogenetic analysis revealed dynamic changes of prolamin gene regions and genetic affinities among Th. elongatum, Triticum aestivum, T. urartu and Aegilops tauschii. The Th. elongatum genome, like the B subgenome of T. aestivum, only contained celiac disease epitope DQ8-glia-α1/DQ8.5-glia-α1, which provided a theoretical basis for the low gluten toxicity wheat breeding. The transcriptome data of Th. elongatum exhibited differential expression in quantity and pattern in the same subfamily or different subfamilies. Dough rheological properties of T. aestivum-Th. elongatum disomic substitution (DS) line 1E(1D) showed higher peak height values than that of their parents, and DS6E(6D) exhibited fewer α-gliadins, which indicates the potential usage for wheat quality breeding. CONCLUSIONS: Overall, this study provided a comprehensive overview of the prolamin gene family in Th. elongatum, and suggested a promising use of this species in the generation of improved wheat breeds intended for the human diet.

Metagenomic analysis revealed the potential role of gut microbiome in gout.

Emerging evidence indicates an association between gut microbiome and arthritis diseases including gout. However, how and which gut bacteria affect host urate degradation and inflammation in gout remains unclear. Here we performed a metagenome analysis on 307 fecal samples from 102 gout patients and 86 healthy controls. Gout metagenomes significantly differed from those of healthy controls. The relative abundances of Prevotella, Fusobacterium, and Bacteroides were increased in gout, whereas those of Enterobacteriaceae and butyrate-producing species were decreased. Functionally, gout patients had greater abundances for genes in fructose, mannose metabolism and lipid A biosynthesis, and lower for genes in urate degradation and short chain fatty acid production. A three-pronged association between metagenomic species, functions and clinical parameters revealed that decreased abundances of species in Enterobacteriaceae were associated with reduced amino acid metabolism and environmental sensing, which together contribute to increased serum uric acid and C-reactive protein levels in gout. A random forest classifier based on three gut microbial genes showed high predictivity for gout in both discovery and validation cohorts (0.91 and 0.80 accuracy), with high specificity in the context of other chronic disorders. Longitudinal analysis showed that uric-acid-lowering and anti-inflammatory drugs partially restored gut microbiota after 24-week treatment. Comparative analysis with obesity, type 2 diabetes, ankylosing spondylitis and rheumatoid arthritis indicated that gout metagenomes were more similar to those of autoimmune than metabolic diseases. Our results suggest that gut dysbiosis was associated with dysregulated host urate degradation and systemic inflammation and may be used as non-invasive diagnostic markers for gout.

Nutrigenomics reveals potential genetic underpinning of diverse taste preference of Chinese men.

BACKGROUND: Taste preference varies geographically in China. However, studies on Chinese people's taste preference in different regions of China are limited, and are lack of research on the mechanism of differences in taste preference, especially in genetics. OBJECTIVE: This study aims to investigate the characteristics of taste preference of Chinese men, and estimate whether diverse taste preference in Chinese have genetic underpinning. METHODS: We conducted a questionnaire survey on taste preferences on 1076 males from 10 regions of China, and collected another 1427 males from the same regions which genotyped by microarray. We compared the correlation between different taste preference, and evaluated the correlation between the mutation frequency of inhouse database and different taste preference. The putative taste-preference-related genes were further utilized to estimate the candidate relationship on gene and gene network in different taste preference. RESULTS: There was a correlation between different taste preferences in Chinese men. We found 31 SNPs associated with 6 kind of taste preferences. These SNPs located within or nearby 36 genes, and the tastes associated with 4 of these genes (TRPV1, AGT, ASIC2 and GLP1R) are consistent with the previous studies. Moreover, in different tastes which were suggested to be associated with each other, some putative related genes were the same or in the same gene network, such as pathways related with blood pressure, response to stimulus and nervous system. CONCLUSIONS: This study indicates that the diverse taste preference of Chinese men may have genetic underpinning.

Comparative Analysis of the Glutathione S-Transferase Gene Family of Four Triticeae Species and Transcriptome Analysis of GST Genes in Common Wheat Responding to Salt Stress.

Glutathione S-transferases (GSTs) are ancient proteins encoded by a large gene family in plants, which play multiple roles in plant growth and development. However, there has been little study on the GST genes of common wheat (Triticum aestivum) and its relatives (Triticum durum, Triticum urartu, and Aegilops tauschii), which are four important species of Triticeae. Here, a genome-wide comprehensive analysis of this gene family was performed on the genomes of common wheat and its relatives. A total of 346 GST genes in T. aestivum, 226 in T. durum, 104 in T. urartu, and 105 in Ae. tauschii were identified, and all members were divided into ten classes. Transcriptome analysis was used to identify GST genes that respond to salt stress in common wheat, which revealed that the reaction of GST genes is not sensitive to low and moderate salt concentrations but is sensitive to severe concentrations of the stressor, and the GST genes related to salt stress mainly come from the Tau and Phi classes. Six GST genes which respond to different salt concentrations were selected and validated by a qRT-PCR assay. These findings will not only provide helpful information about the function of GST genes in Triticeae species but also offer insights for the future application of salt stress resistance breeding in common wheat.

Metabolomics and gene expression analysis reveal the accumulation patterns of phenylpropanoids and flavonoids in different colored-grain wheats (Triticum aestivum L.).

Colored-grain wheats have received increasing attention owing to their high nutritional values. In this study, we compared the metabolomes of four pigmented wheat cultivars with conventional yellow wheat using an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS)-based metabolomics approach. A total of 711 metabolites were identified, and considerable differences were observed in the flavonoid and phenylpropanoid metabolites among five samples by orthogonal signal correction and partial least squares-discriminant analysis (OPLS-DA) analysis. These differential metabolites were significantly enriched in the "anthocyanin biosynthesis", "flavones and flavonols biosynthesis", and "flavonoids biosynthesis" pathways. Furthermore, the expression of 9 structural genes and 2 regulatory genes involved in flavonoid biosynthesis pathway were investigated by quantitative real-time PCR (qRT-PCR). Results suggested that blue, red, purple, and black wheat cultivars showed higher transcription levels of structural and regulatory genes in the flavonoid pathway than that of conventional yellow wheat, possibly accounting for the abundant anthocyanin accumulation in the grains of these four cultivars. This study laid a foundation for understanding the accumulation of flavonoids and coloration mechanisms in colored-grain wheats, and provides a theoretical basis for their sufficient utilization.

Distinct nucleotide patterns among three subgenomes of bread wheat and their potential origins during domestication after allopolyploidization.

BACKGROUND: The speciation and fast global domestication of bread wheat have made a great impact on three subgenomes of bread wheat. DNA base composition is an essential genome feature, which follows the individual-strand base equality rule and [AT]-increase pattern at the genome, chromosome, and polymorphic site levels among thousands of species. Systematic analyses on base compositions of bread wheat and its wild progenitors could facilitate further understanding of the evolutionary pattern of genome/subgenome-wide base composition of allopolyploid species and its potential causes. RESULTS: Genome/subgenome-wide base-composition patterns were investigated by using the data of polymorphic site in 93 accessions from worldwide populations of bread wheat, its diploid and tetraploid progenitors, and their corresponding reference genome sequences. Individual-strand base equality rule and [AT]-increase pattern remain in recently formed hexaploid species bread wheat at the genome, subgenome, chromosome, and polymorphic site levels. However, D subgenome showed the fastest [AT]-increase across polymorphic site from Aegilops tauschii to bread wheat than that on A and B subgenomes from wild emmer to bread wheat. The fastest [AT]-increase could be detected almost all chromosome windows on D subgenome, suggesting different mechanisms between D and other two subgenomes. Interestingly, the [AT]-increase is mainly contributed by intergenic regions at non-selective sweeps, especially the fastest [AT]-increase of D subgenome. Further transition frequency and sequence context analysis indicated that three subgenomes shared same mutation type, but D subgenome owns the highest mutation rate on high-frequency mutation type. The highest mutation rate on D subgenome was further confirmed by using a bread-wheat-private SNP set. The exploration of loci/genes related to the [AT] value of D subgenome suggests the fastest [AT]-increase of D subgenome could be involved in DNA repair systems distributed on three subgenomes of bread wheat. CONCLUSIONS: The highest mutation rate is detected on D subgenome of bread wheat during domestication after allopolyploidization, leading to the fastest [AT]-increase pattern of D subgenome. The phenomenon may come from the joint action of multiple repair systems inherited from its wild progenitors.

Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population.

Tobacco use is one of the leading causes of preventable disease worldwide. Genetic studies have elucidated numerous smoking-associated risk loci in American and European populations. However, genetic determinants for cigarette smoking in Chinese populations are under investigated. In this study, a whole-genome sequencing (WGS)-based genome-wide association study (GWAS) was performed in a Chinese Han population comprising 620 smokers and 564 nonsmokers. Thirteen single-nucleotide polymorphisms (SNPs) of the raftlin lipid linker 1 (RFTN1) gene achieved genome-wide significance levels (P < 5 x 10-8) for smoking initiation. The rs139753473 from RFTN1 and six other suggestively significant loci from CUB and sushi multiple domains 1 (CSMD1) gene were also associated with cigarettes per day (CPD) in an independent Chinese sample consisting of 1,329 subjects (805 smokers and 524 nonsmokers). When treating males separately, associations between smoking initiation and PCAT5/ANKRD30A, two genes involved in cancer development, were identified and replicated. Within RFTN1, two haplotypes (i.e., C-A-C-G and A-G-T-C) formed by rs796812630-rs796584733-rs796349027-rs879511366 and three haplotypes (i.e., T-T-C-C-C, T-T-A-T-T, and C-A-A-T-T) formed by rs879401109-rs879453873-rs75180423-rs541378415-rs796757175 were strongly associated with smoking initiation. In addition, we also revealed two haplotypes (i.e., C-A-G-G and T-C-T-T derived from rs4875371-rs4875372-rs17070935-rs11991366) in the CSMD1 gene showing a significant association with smoking initiation. Further bioinformatics functional assessment suggested that RFTN1 may participate in smoking behavior through modulating immune responses or interactions with the glucocorticoid receptor alpha and the androgen receptor. Together, our results may help understand the mechanisms underlying smoking behavior in the Chinese Han population.

A Chromosome-Level Genome Assembly of Dendrobium Huoshanense Using Long Reads and Hi-C Data.

Dendrobium huoshanense is used to treat various diseases in traditional Chinese medicine. Recent studies have identified active components. However, the lack of genomic data limits research on the biosynthesis and application of these therapeutic ingredients. To address this issue, we generated the first chromosome-level genome assembly and annotation of D. huoshanense. We integrated PacBio sequencing data, Illumina paired-end sequencing data, and Hi-C sequencing data to assemble a 1.285 Gb genome, with contig and scaffold N50 lengths of 598 kb and 71.79 Mb, respectively. We annotated 21,070 protein-coding genes and 0.96 Gb transposable elements, constituting 74.92% of the whole assembly. In addition, we identified 252 genes responsible for polysaccharide biosynthesis by Kyoto Encyclopedia of Genes and Genomes functional annotation. Our data provide a basis for further functional studies, particularly those focused on genes related to glycan biosynthesis and metabolism, and have implications for both conservation and medicine.

Horizontal gene transfer of Fhb7 from fungus underlies Fusarium head blight resistance in wheat.

Fusarium head blight (FHB), a fungal disease caused by Fusarium species that produce food toxins, currently devastates wheat production worldwide, yet few resistance resources have been discovered in wheat germplasm. Here, we cloned the FHB resistance gene Fhb7 by assembling the genome of Thinopyrum elongatum, a species used in wheat distant hybridization breeding. Fhb7 encodes a glutathione S-transferase (GST) and confers broad resistance to Fusarium species by detoxifying trichothecenes through de-epoxidation. Fhb7 GST homologs are absent in plants, and our evidence supports that Th. elongatum has gained Fhb7 through horizontal gene transfer (HGT) from an endophytic Epichloë species. Fhb7 introgressions in wheat confers resistance to both FHB and crown rot in diverse wheat backgrounds without yield penalty, providing a solution for Fusarium resistance breeding.

Molecular Dissection of TaLTP1 Promoter Reveals Functional Cis-Elements Regulating Epidermis-Specific Expression.

Plant epidermis serves important functions in shoot growth, plant defense and lipid metabolism, though mechanisms of related transcriptional regulation are largely unknown. Here, we identified cis-elements specific to shoot epidermis expression by dissecting the promoter of Triticum aestivum lipid transfer protein 1 (TaLTP1). A preliminary promoter deletion analysis revealed that a truncated fragment within 400 bp upstream from the translation start site was sufficient to confer conserved epidermis-specific expression in transgenic Brachypodium distachyon and Arabidopsis thaliana. Further, deletion or mutation of a GC(N4)GGCC motif at position -380 bp caused a loss of expression in pavement cells. With an electrophoretic mobility shift assay (EMSA) and transgenic reporter assay, we found that a light-responsive CcATC motif at position -268 bp was also involved in regulating pavement cell-specific expression that is evolutionary conserved. Moreover, expression specific to leaf trichome cells was found to be independently regulated by a CCaacAt motif at position -303 bp.

Sympatric speciation of wild emmer wheat driven by ecology and chromosomal rearrangements.

In plants, the mechanism for ecological sympatric speciation (SS) is little known. Here, after ruling out the possibility of secondary contact, we show that wild emmer wheat, at the microclimatically divergent microsite of "Evolution Canyon" (EC), Mt. Carmel, Israel, underwent triple SS. Initially, it split following a bottleneck of an ancestral population, and further diversified to three isolated populations driven by disruptive ecological selection. Remarkably, two postzygotically isolated populations (SFS1 and SFS2) sympatrically branched within an area less than 30 m at the tropical hot and dry savannoid south-facing slope (SFS). A series of homozygous chromosomal rearrangements in the SFS1 population caused hybrid sterility with the SFS2 population. We demonstrate that these two populations developed divergent adaptive mechanisms against severe abiotic stresses on the tropical SFS. The SFS2 population evolved very early flowering, while the SFS1 population alternatively evolved a direct tolerance to irradiance by improved ROS scavenging activity that potentially accounts for its evolutionary fate with unstable chromosome status. Moreover, a third prezygotically isolated sympatric population adapted on the abutting temperate, humid, cool, and forested north-facing slope (NFS), separated by 250 m from the SFS wild emmer wheat populations. The NFS population evolved multiple resistant loci to fungal diseases, including powdery mildew and stripe rust. Our study illustrates how plants sympatrically adapt and speciate under disruptive ecological selection of abiotic and biotic stresses.

High-throughput sequencing reveals the diversity of TCR ß chain CDR3 repertoire in patients with severe acne.

Acne is a common chronic inflammatory skin disease, and the inflammation immune response runs through all stages of acne lesions. In this study, we use a combination of multiplex-PCR and high-throughput sequencing technologies to analyze T cell receptor ß chain CDR3 (complementarity-determining region 3) in peripheral blood isolated from severe acne patients. Once compared with healthy controls, we propose to identify acne-relevant CDR3 peptides. Our results reveal that the diversity of T cell receptor ß chain (TRB) CDR3 sequences in the peripheral blood of the severe acne vulgaris (SA) group differed from that of the control group. In addition, we find 10 TRB CDR3 sequences, amino acid sequences and V-J combinations with significantly different expressions between the SA group and the non-acne (NA) group (P < 0.0001). These findings may contribute to a better understanding of the role of immunity in the pathogenesis of acne and may serve as biomarkers for evaluating risk or prognosis of severe acne disease in future.

A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome.

An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.