Putative Genes Research Articles

Discover QTLs for the level of blood components in Shaoxing duck using GWAS and haplotype sharing analysis

Blood composition is indicative of health-related traits such as immunity and metabolism. The use of molecular genetics to investigate alterations in these attributes in laying ducks is a novel approach. Our objective was to employ genome − wide association studies (GWAS) and haplotype − sharing analysis to identify genomic regions and potential genes associated with 11 blood components in Shaoxing ducks. Our findings revealed 35 SNPs and 1 SNP associated with low-density lipoprotein cholesterol (LDL) and globulin (GLB), respectively. We identified 36 putative candidate genes for the LDL trait in close proximity to major QTLs and key loci. Based on their biochemical and physiological properties, TRA2A, NPY, ARHGEF26, DHX36, and AADAC are the strongest putative candidate genes. Through linkage disequilibrium analysis and haplotype sharing analysis, we identified three haplotypes and one haplotype, respectively, that were significantly linked with LDL and GLB. These haplotypes could be selected as potential candidate haplotypes for molecular breeding of Shaoxing ducks. Additionally, we utilized a bootstrap test to verify the reliability of GWAS with small experimental samples. The test can be accessed at https://github.com/xuwenwu24/Bootstrap-test.

Ancestry and genome-wide association study of domestic pigs that survive African swine fever in Uganda

African swine fever (ASF) is endemic to Uganda and causes annual outbreaks. Some pigs survive these outbreaks and remain asymptomatic but are African swine fever virus (ASFV) positive. The potential heritability and genetic disparities in disease susceptibility among Ugandan pigs are not fully understood. In a 12-year study, whole blood and tissue samples were collected from 212 pigs across 19 districts in Uganda. Polymerase chain reaction (PCR) assays were used to determine ASFV infection status and genotyping was completed using a commercial porcine array. The point prevalence of ASF was calculated for each district, and breed composition origins were quantified for the sampled pigs by implementing established ancestry analyses. Genome-wide associated studies (GWAS) were conducted using all available domestic swine samples (full study population; n = 206) as well as a reduced dataset (farm-level study population; n = 129). This study revealed a greater number of ASFV-positive pigs in border districts than in non-border districts, a high level of admixture among domestic pigs sampled from Ugandan smallholder farms, and 48 loci that were associated with ASFV infection status. The discovery of 48 significant SNPs and 28 putative candidate genes may imply the possibility of heritability for resistance to ASFV. However, additional investigations in ASFV-endemic regions are required to fully elucidate the heritability of ASFV susceptibility among surviving pigs in Uganda.

Draft genome sequence of a cyanobacterium Gloeocapsa sp. BRSZ, isolated from Bo Khlueng hot spring in Ratchaburi, Thailand.

We report the draft genome sequence of Gloeocapsa sp. BRSZ isolated from Bo Khlueng hot spring in Thailand, comprising 42 contigs assembled at the scaffold level, totaling 6,084,403 bp, with 43.5% G + C content. It contains 5,456 putative protein-coding genes, including genes responsible for biosynthesis of mycosporine-like amino acids.

Functional genomics implicates natural killer cells in the pathogenesis of ankylosing spondylitis

Multiple lines of evidence indicate that ankylosing spondylitis (AS) is a lymphocyte-driven disease. However, which lymphocyte populations are critical in AS pathogenesis is not known. In this study, we aimed to identify the key cell types mediating the genetic risk in AS using an unbiased functional genomics approach. We integrated genome-wide association study (GWAS) data with epigenomic and transcriptomic datasets of human immune cells. To quantify enrichment of cell type-specific open chromatin or gene expression in AS risk loci, we used three published methods - LDSC-SEG, SNPsea, scDRS - that have successfully identified relevant cell types in other diseases. Natural killer (NK) cell-specific open chromatin regions are significantly enriched in heritability for AS, compared to other immune cell types such as T cells, B cells, and monocytes. This finding was consistent between two AS GWAS. Using RNA-seq data, we validated that genes in AS risk loci are enriched in NK cell-specific gene expression. Using the human Space-Time Gut Cell Atlas, we also found significant upregulation of AS-associated genes predominantly in NK cells. We performed co-localization analyses between GWAS risk loci and genetic variants associated with gene expression (eQTL) to find putative target genes. This revealed four AS risk loci affecting regulation of candidate target genes in NK cells: two known loci, ERAP1 and TNFRSF1A, and two under-studied loci, ENTR1 (aka SDCCAG3) and B3GNT2. Our findings suggest that NK cells may play a crucial role in AS development and highlight four putative target genes for functional follow-up in NK cells.

Association of genetically predicted human metabolomic gene expression with incident heart failure

Abstract Background Heart failure (HF) represents a significant challenge both for patients and healthcare systems worldwide. Despite ongoing efforts, therapeutic options are limited. The underlying pathophysiology involves intricate changes in cardiac metabolism that strongly influence the clinical phenotype, thus potentially offering novel options for therapeutic targeting. Systematic prioritisation of metabolic genes regarding their phenotypic impact on HF is outstanding. Purpose We investigate the association of genetically predicted metabolic gene expression with the onset of HF within UK Biobank (UKB). We followed up on identified candidate genes using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) models of cardiomyocyte hypertrophy. Methods Utilising genomic data of 484,372 UKB participants and left ventricle-specific expression quantitative trait loci (eQTL) information from Genotype-Tissue Expression (GTEx) project, we predicted genetically regulated gene expression using established methods (PrediXcan) for all metabolic genes. Subsequently, we employed per-gene Cox proportional hazards (COX-PH) models to assess the association of genetically predicted metabolic gene expression with incident HF. We adjusted models for clinical risk using established risk models (Pooled Cohort Equations to Prevent HF (PCP-HF)). To validate our findings in vitro, we subjected hiPSC-CMs to a sympathomimetic stimulus via treatment with endothelin-1 (ET-1; 10 nM). We evaluate alterations in expression via real-time quantitative polymerase chain reaction (RT-qPCR) and establish methods for assessing hypertrophic remodelling. Results COX-PH models revealed the predicted expression of 104/1515 metabolic genes to be independently associated with the onset of HF. Subsequent refinement with a meta-analysis of commonly dysregulated genes in end-stage HF narrowed our findings to 46 candidate genes, of which several were known for their role in HF pathophysiology. We further traced nine genes for validation in hiPSC-CM models and showed significant dysregulation of several genes following the treatment with ET-1. Flow cytometry measured hiPSC-CM hypertrophy following sympathomimetic stimulation (p=0.036). Extracellular flux analysis revealed canonical changes following treatment with ET-1. Conclusions The study revealed several metabolic genes associated with incident HF, thus confirming previous findings and highlighting novel, putative therapeutic target genes. We confirmed transcriptional changes in an in vitro model. Ongoing work includes further validation via silencing candidate genes in hiPSC-CMs and subjection to the established phenotypic in vitro models.

Early Steps of the Biosynthesis of the Anticancer Antibiotic Pleurotin.

Pleurotin is a meroterpenoid specialized metabolite made by the fungus Hohenbuehelia grisea, and it is a lead anticancer molecule due to its irreversible inhibition of the thioredoxin-thioredoxin reductase system. Total synthesis of pleurotin has been achieved, including through a stereoselective route; however, its biosynthesis has not been characterized. In this study, we used isotope-labeled precursor feeding to show that the nonterpenoid quinone ring of pleurotin and its congeners is derived from phenylalanine. We sequenced the genome of H. grisea and used comparative transcriptomics to identify putative genes involved in pleurotin biosynthesis. We heterologously expressed a UbiA-like prenyltransferase from H. grisea that led to the accumulation of the first predicted pleurotin biosynthetic intermediate, 3-farnesyl-4-hydroxybenzoic acid. This work sets the foundation to fully elucidate the biosynthesis of pleurotin and its congeners, with long-term potential to optimize their production for therapeutic use and engineer the pathway toward the biosynthesis of valuable analogues.

Comprehensive analysis of transcription factor binding sites and expression profiling of rice pathogenesis related genes (OsPR1)

Pathogenesis-related (PR) proteins, found in plants, play a crucial role in responding to both biotic and abiotic stresses and are categorized into 17 distinct families based on their properties and functions. We have conducted a phylogenetic analysis of OsPR1 genes (rice PR1 genes) in conjunction with 58 putative PR1 genes identified in Brachypodium distachyon, Hordeum vulgare, Brassica rapa, and Zea mays through BLASTP predictions. We extensively investigated the responses of the remaining 11 rice PR1 genes, using OsPR1a as a reference, under various stress conditions, including phytohormone treatments (salicylic acid and brassinosteroid [BR]), wounding, and heat stress (HS). In rice, of the 32 predicted OsPR1 genes, 12 have been well-characterized for their roles in disease resistance, while the functions of the remaining genes have not been studied extensively. In our study, we selected an additional 11 OsPR1 genes for further analysis and constructed a phylogenetic tree based on the presence of a 10-amino-acid-long conserved motif within these proteins. The phylogenetic analysis revealed that both OsPR1a from earlier studies and OsPR1-74 from our current study belong to the same clade. These genes consistently exhibit upregulation in response to diverse stress treatments such as biotic stress and abiotic stresses such as heat, drought, and salinity, indicating their potential roles in enhancing stress tolerance in rice. Significantly, this study delves into the previously unexplored role of OsPR1 genes in responding to Brassinosteroid (BR) and heat stress (HS) treatments, confirming their involvement in stress responses through qRT-PCR analysis. We found that seven genes were upregulated by EBR treatment. During heat stress (HS), six and seven genes were upregulated at 1hand 4h HS, respectively. The remaining genes OsPR1-22 and OsPR1-75 were upregulated at 1h but downregulated at 4h HS and under EBR treatment. In contrast, OsPR1-76 was upregulated at both 1h and 4h HS, but downregulated under EBR treatment. Promoters of PR1 genes in rice and other crops are rich in transcription factor binding sites (TFBSs) and feature a conserved Cysteine-rich secretory protein (SCP or CAP) motif. This study advances our understanding of PR1 gene regulation and its potential to enhance stress tolerance in rice.

Genome-wide association study reveals effect of nsSNPs on candidate genes in rice during iron deficiency.

Resource-poor areas with moisture deficit lands following aerobic and direct seeded rice (DSR) methods of cultivation face severe problems of iron deficiency. In this study, Bengal and Assam Aus rice panel was phenotyped at the seedling stage using an iron-deprived hydroponic medium for various shoot and root traits. A novel iron deficiency scoring scale was used to classify the tolerance reaction and could range anywhere between 0 and 9, indicating the most tolerant and susceptible, respectively. The GWAS results identified four putative candidate genes; OsFLA for number of leaves and shoot length, OsBIDK1 for root traits; average diameter, volume, biomass, projected area, and surface area, OsHPL3 for chlorophyll index of the third leaf and AKR2B (XBOS252) was for Fe score, (which was earlier reported in relation to Xa21). The nsSNP (nsSNPs) variations in these gene sequences were used to group the panel and identify superior haplotypes and donors. BR16 was identified as a superior donor, with higher chlorophyll index and shoot length than RA23, also higher values for root traits like root average diameter, root volume, root projected area and root surface area followed by Shete Bhado. The impact of identified nsSNPs on protein structure and stability was investigated. The conserved domains detected in the mutated proteins of the superior haplotypes are very informative, highlighting that natural selection favors abiotic stress tolerant variants in resource poor areas. Thus, justifying our choice of Aus landraces for association mapping of Fe deficiency tolerant genes in rice.

Identification of putative genes for caffeoylated flavonoid glycoside biosynthesis in Pseudognaphalium affine

Pseudognaphalium affine (D. Don) Anderberg, commonly found in East Asia, has extensive applications as both a traditional medicine and a vegetable in China. The caffeoylated flavonoid glycosides produced by P. affine exhibit remarkable anti-complement activities. Although these compounds have potential therapeutic value, the biosynthetic pathway responsible for their production remains largely unknown. To elucidate the key catalytic steps involved in caffeoylated flavonoid glycoside biosynthesis, we conducted a comprehensive analysis of the full-length transcriptome of P. affine. Further phylogenetic tree analysis predicted potential UDP glycosyltransferase (UGT) and BAHD acyltransferase (BAHD-AT) related with caffeoylated flavonoid glycoside biosynthesis. Subsequently, enzyme assay led to the discovery of PaUGT23 as a key enzyme responsible for the glycosylation of hydroxy groups in flavonoids, resulting in the formation of luteolin-4′-O-glucoside, luteolin-7-O-glucoside, quercetin-4′-O-glucoside, quercetin-7-O-glucoside, and apigenin-7-O-glucoside, while PaBAHD21 was found to catalyze the caffeoylation of flavonoid glycosides, resulting in the formation of luteolin 4′-O-β-D-(6″-E-caffeoyl)-glucopyranoside, quercetin 4′-O-β-D-(6″-E-caffeoyl)-glucopyranoside, apigenin 4′-O-β-D-(6″-E-caffeoyl)-glucopyranoside and apigenin 7-O-β-D-(6″-E-caffeoyl)-glucopyranoside. Moreover, their catalytic activities were verified in vivo by transient transfection experiment. This study presents the first comprehensive analysis of the full-length transcriptome in P. affine, providing significant insights into the biosynthesis and accumulation mechanisms of bioactive caffeoylated flavonoid glycosides.

Chemosensory function of Varroa gnathosoma: transcriptomic and proteomic analyses.

In this study, we evaluated the role of the gnathosoma (mouthparts) in chemosensing of the most devastating honey bee parasite, Varroa destructor mite. Through transcriptomic analysis, we compared the expression of putative chemosensory genes between the body parts containing the main chemosensory organs (the forelegs), gnathosoma and the rest of the body devoid of these two body parts. Furthermore, we checked the presence of chemosensory-related transcripts in the proteome of the gnathosoma. Our comparative transcriptomic analysis revealed the presence of 83 transcripts with known characteristic conserved domains belonging to eight chemosensory gene families in the three Varroa transcriptomes. Among these transcripts, 11 were significantly upregulated in the mite's forelegs, compared to 8 and 10 in the gnathosoma and body devoid of both organs, respectively. Whilst the gnathosoma and the forelegs share similar expression of some putative lipid carrier proteins, membrane-bound receptors, and associated proteins, they also differ in the expression profiles of some transcripts belonging to these protein families. This suggests two functional chemosensory organs that may differ in their chemosensory function according to specific characteristics of compounds they detect. Moreover, the higher expression of some chemosensory transcripts in the body devoid of forelegs and gnathosoma compared to the gnathosoma alone, may suggest the presence of additional function of these transcripts or alternatively presence of additional external or internal chemosensory organs. Insights into the functional annotation of a highly expressed gustatory receptor present in both organs using RNA interference (RNAi) are also revealed.

Exploring the Effect of Active Components in Oil Tree Peony Seed Meal on Swine Disease Resistance and its Potential Mechanisms Based on Network Pharmacology and Molecular Docking.

This study aims to explore the feasibility of using network pharmacology and molecular docking technology to predict the effects of active components from oil tree peony seed meal (PSM) on swine diseases. Ten active components of PSM were screened Screening through literature search and network pharmacology standards, including Betulinic acid, Quercetin, Kaempferol, Luteolin, Isorhamnetin, Hydroxygenkwanin, Hederagenin, Benzoyl Paeoniflorin, Albiflorin, Paeoniflorin. Ten types of swine diseases were selected, including African Swine Fever, Aftosa, Swine Vesicular Disease, Transmissible Gastroenteritis, Swine Streptococcal Infection, Blue Aural Disease, Swine Infectious Atrophic Rhinitis, Swine Influenza, Swine Erysipelas, Swine Epidemic Encephalitis. The results showed that the average number of cross genes between the potential target genes of PSM active components and each swine disease target gene accounted for 7.64 % of the total number of swine disease target genes. The GO enrichment analyses showed that putative targets exist in endosomes, lysosomes, cell membranes, nerves, growth factor activity, receptor tyrosine kinase binding, enzyme binding, growth factor binding, transcription coactivator binding, oxidoreductase activity, prostaglandin E receptor activity and insulin receptor substrate binding. The KEGG enrichment analysis results showed that these putative genes were involved in various cancer progression pathways, signaling pathways, and hormone regulatory pathways. A total of 8 core targets were obtained through protein-protein interaction networks analysis, including Protein Kinase CAMP-Activated Catalytic Subunit Alpha (PRKACA), Non-Receptor Tyrosine Kinase (SRC), Mitogen-Activated Protein Kinase 1 (MAPK1), E1A Binding Protein P300 (EP300), Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A), Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta (PIK3CB), C-X-C chemokine receptor type 4 (CXCR4) and Estrogen Receptor 2 (ESR2). The HIF-1 signaling pathway was found to be associated with all 10 selected swine diseases. The PD-L1 expression, and PD-1 checkpoint pathway in cancer, and thyroid hormone signaling pathway were not only enriches the core target with a quantity of 7, but also associated with 9 Swine diseases. In addition, the molecular docking results indicate that the core ingredients have strong affinity with hub genes. The research suggests that the active components of PSM may intervene in swine diseases through multiple components, targets, and pathways.

Discovering a novel glycosyltransferase gene CmUGT1 enhances main metabolites production of Cordyceps militaris

Cordyceps militaris is a filamentous fungus used for both medicinal and culinary purposes. It exhibits a wide range of pharmacological activities due to its valuable contents of cordycepin, polysaccharides, carotenoids, terpenoids and other metabolites. However, C. militaris strains are highly susceptible to irreversible degradation in agricultural production, which is often manifested as a prolonged color change period and a significant decrease in the production of secondary metabolites. UDP-glycosyltransferases are an important enzyme family that participates in the synthesis of terpenoids by performing the glycosylation of key residues of enzymes or molecules. However, few studies have focused on its effect on the regulation of metabolite production in C. militaris. Therefore, in this study, we performed transcriptome analysis across four different developmental stages of C. militaris to target the putative glycosyltransferase gene CmUGT1, which plays important roles in metabolite production. We further constructed and screened a CmUGT1-overexpressing strain by Agrobacterium tumefaciens-mediated infestation of C. militaris spores. The major metabolite production of the wild-type and CmUGT1-overexpressing C. militaris strains was determined after short-term shake-flask cultivation of mycelia. The results showed that the yields of carotenoids and polysaccharides in the mycelia of the CmUGT1-overexpressing strains were 3.8 and 3.4 times greater than those in the mycelia of the wild type, respectively (p < 0.01). The levels of intracellular and extracellular cordycepin produced by the overexpression strain were 4.4 and 8.0 times greater than those produced by the wild-type strain (p < 0.01). This suggests that the overexpression of CmUGT1 in C. militaris enhances the synthesis activities of the main enzymes related to metabolite production, which provides a guide for obtaining excellent recombinant strains of C. militaris.

Integrative Human Genetic and Cellular Analysis of the Pathophysiological Roles of AnxA2 in Alzheimer's Disease.

Alzheimer's disease (AD) is an intractable and progressive neurodegenerative disease. Amyloid beta (Aβ) aggregation is the hallmark of AD. Aβ induces neurotoxicity through a variety of mechanisms, including interacting with membrane receptors to alter downstream signaling, damaging cellular or organelle membranes, interfering with protein degradation and synthesis, and inducing an excessive immune-inflammatory response, all of which lead to neuronal death and other pathological changes associated with AD. In this study, we extracted gene expression profiles from the GSE5281 and GSE97760 microarray datasets in the GEO (Gene Expression Omnibus) database, as well as from the Human Gene Database. We identified differentially expressed genes in the brain tissues of AD patients and healthy persons. Through GO, KEGG, and ROC analyses, annexin A2 (AnxA2) was identified as a putative target gene. Notably, accumulating evidence suggests that intracellular AnxA2 is a key regulator in various biological processes, including endocytosis, transmembrane transport, neuroinflammation, and apoptosis. Thus, we conducted a series of cell biology experiments to explore the biological function of AnxA2 in AD. The results indicate that AnxA2 gene knockdown primarily affects oxidative phosphorylation, cell cycle, AD, protein processing in the endoplasmic reticulum, SNARE interactions in vesicular transport, and autophagy. In SH-SY5Y cells secreting Aβ42, AnxA2 gene knockdown exacerbated Aβ42-induced cytotoxicity, including cell death, intracellular ROS levels, and neuronal senescence, altered cell cycle, and reduced ATP levels, suggesting its critical role in mitochondrial function maintenance. AnxA2 gene knockdown also exacerbated the inhibitory effect of Aβ42 on cell migration. AnxA2 overexpression reduced the inflammatory response induced by Aβ42, while its absence increased pro-inflammatory and decreased anti-inflammatory responses. Furthermore, AnxA2 gene knockdown facilitated apoptosis and decreased autophagy. These results indicated potential pathophysiological roles of AnxA2 in AD.

Mapping lineage-traced cells across time points with moslin

Simultaneous profiling of single-cell gene expression and lineage history holds enormous potential for studying cellular decision-making. Recent computational approaches combine both modalities into cellular trajectories; however, they cannot make use of all available lineage information in destructive time-series experiments. Here, we present moslin, a Gromov-Wasserstein-based model to couple cellular profiles across time points based on lineage and gene expression information. We validate our approach in simulations and demonstrate on Caenorhabditis elegans embryonic development how moslin predicts fate probabilities and putative decision driver genes. Finally, we use moslin to delineate lineage relationships among transiently activated fibroblast states during zebrafish heart regeneration.

Characterization and genomic analysis of phage vB_SmaP_c9-N, a novel Stenotrophomonas maltophilia podophage with antibiofilm activity.

Stenotrophomonas maltophilia strains are increasingly emerging as multidrug-resistant pathogens. Moreover, S. maltophilia commonly produces biofilms that enhance antibiotic resistance in bacteria. Phages are effective alternative drugs for treating S. maltophilia infections. In this study, the lytic phage vB_SmaP_c9-N (abbreviated as Φc9-N), which is specific for S. maltophilia, was isolated from Nanhu Lake, Wuhan, China. Electron microscopy observation revealed that Φc9-N is a podophage. Φc9-N is stable over a wide pH range, from pH 4 to 10, and its activity did not change after storage at 4°C for 2months. The latency period of Φc9-N is 5 min, and its outbreak period is 35min. Antibacterial tests showed that Φc9-N could effectively inhibit the growth of S. maltophilia c24. Moreover, the biofilm production of S. maltophilia c24 decreased when Φc9-N was administered either to the forming biofilm or to the mature biofilm. These results suggest that Φc9-N has application potential in clinical treatment. The genome of Φc9-N is a dsDNA of 43,170 bp with 55 putative unidirectional genes, 18 of which were assigned putative functions, while other genes encoded hypothetical proteins. Genome sequence comparisons and phylogenetic analysis indicated that Φc9-N represents a new species, and, together with the Stenotrophomonas phages BUCT700, BUCT703, BUCT598, and vB_SmaS_P15, can be included in the newly proposed genus "Maltovirus" in the family Autographiviridae.

Pseudomonas koreensis AB36 from a gold mine: genomic insights into adaptation to extreme conditions and potential plant growth promotion

AbstractThe genus Pseudomonas is one of the most varied and widespread bacterial genera, with species found in most environment. They are known to degrade organic and inorganic compounds, produce secondary metabolites, and enhance plant growth. The genome of Pseudomonas koreensis AB36, a heavy metal resistant organism isolated from a gold mine was sequenced to unveil the versatile metabolic potential of the organism. The genome is a single circular chromosome of 5,902,614 bp, with G + C content of 60.1%. There are 4154 similar orthologous gene clusters shared among strain AB36 and other sequenced P. koreensis strains with 7 clusters found alone in the genome of strain AB36. Genome mining of the organism predicted 8 biosynthetic gene clusters using antiSMASH including three non-ribosomal peptide synthethase (NRPS) clusters, arylpolyene and bacteriocin. The genome contains putative genes for heavy metal transport/resistance. These results show the heavy metal resistance ability and degradation of xenobiotic compounds of strain AB36 as well as its potential to adapt to various environments.

Metagenomic profiling of cecal microbiota and antibiotic resistome in rodents

The rodent gut microbiota is a known reservoir of antimicrobial resistance, yet the distribution of antibiotic resistance genes (ARGs) within rodent cecal microbial communities and the specific bacterial species harboring these ARGs remain largely underexplored. This study employed high-throughput sequencing of 122 samples from five distinct rodent species to comprehensively profile the diversity and distribution of ARGs and to identify the bacterial hosts of these genes. A gene catalog of the rodent cecal microbiome was constructed, comprising 22,757,369 non-redundant genes. Analysis of the microbial composition and diversity revealed that Bacillota and Bacteroidota were the dominant bacterial phyla across different rodent species, with significant variations in species composition among the rodents. In total, 3703 putative antimicrobial resistance protein-coding genes were identified, corresponding to 392 unique ARG types classified into 32 resistance classes. The most enriched ARGs in the rodent cecal microbiome were associated with multidrug resistance, followed by glycopeptide and elfamycin antibiotics. Procrustes analysis demonstrated a correlation between the structure of the microbial community and the resistome. Metagenomic assembly-based host tracking indicated that most ARG-carrying contigs originated from the bacterial family Oscillospiraceae. Additionally, 130 ARGs showed significant correlations with mobile genetic elements. These findings provide new insights into the cecal microbiota and the prevalence of ARGs across five rodent species. Future research on a wider range of wild rodent species carrying ARGs will further elucidate the mechanisms underlying the transmission of antimicrobial resistance.

Exploring the mechanism of Danggui Sini Decoction in the treatment of myocardial infarction: A systematic review, network pharmacology, and molecular docking.

Myocardial infarction (MI) is one of the leading causes of death worldwide because of its high morbidity and mortality. Traditional Chinese Medicine compounds play a crucial role in preventing cardiovascular diseases. Danggui Sini Decoction (DSD) is widely used clinically for cardiovascular diseases. However, the mechanism, main components, and main targets of DSD in treating MI are still unclear. In this study, we utilized network pharmacology and molecular docking for exploration. MI-related genes were examined using the Genecards database, and the active ingredients of DSD were screened based on System Pharmacology Database and Analysis Platform of Traditional Chinese Medicine by oral bioavailability ≥ 30% and drug-likeness ≥ 0.18. The protein-protein interaction network diagram was generated using the STRING database. The DAVID web platform was used to carry out gene ontology and Kyoto encyclopedia of gene and genome signaling pathway analysis. DSD's screening study revealed 120 primary active ingredients and 561 putative active target genes. The main therapeutic targets were TP53, EGFR, AKT1, IL6, TNF, STAT3, IL1B, CTNNB1, SRC, MYC, JUN, and INS. Gene ontology and Kyoto encyclopedia of gene and genome analyses revealed that DSD treatment of MI mainly involves the positive regulation of the ERK1 and ERK2 cascades, positive regulation of cell proliferation, inflammatory responses, aging, and the MAPK cascade, along with other biological processes. The molecular docking results indicate that DSD drugs may interact with AKT1, EGFR, TP53, and TNF through formononetin, isorhamnetin, β-Sitosterol, and kaempferol, potentially contributing to the treatment of MI. By utilizing a multi-component, multi-pathway, and multi-target mode of action, DSD may have the potential to prevent MI.

Genome-wide association study of salt tolerance at the seed germination stage in lettuce.

Developing lettuce varieties with salt tolerance at the seed germination stage is essential since lettuce seeds are planted half an inch deep in soil where salt levels are often highest in the salinity-affected growing regions. Greater knowledge of genetics and genomics of salt tolerance in lettuce will facilitate breeding of improved lettuce varieties with salt tolerance. Accordingly, we conducted a genome-wide association study (GWAS) in lettuce to identify marker-trait association for salt tolerance at the seed germination stage. The study involved 445 diverse lettuce accessions and 56,820 single nucleotide polymorphism (SNP) markers obtained through genotype-by-sequencing technology using lettuce reference genome version v8. GWAS using two single-locus and three multi-locus models for germination rate (GR) under salinity stress, 5 days post seeding (GR5d_S) and a salinity susceptibility index (SSI) based on GR under salinity stress and control conditions, 5 days post seeding (SSI_GR5d) revealed 10 significant SNPs on lettuce chromosomes 2, 4, and 7. The 10 SNPs were associated with five novel QTLs for salt tolerance in lettuce, explaining phenotyping variations of 5.85%, 4.38%, 4.26%, 3.77%, and 1.80%, indicating the quantitative nature of these two salt tolerance-related traits. Using the basic local alignment search tool (BLAST) within 100 Kb upstream and downstream of each of the 10 SNPs, we identified 25 salt tolerance-related putative candidate genes including four genes encoding for major transcription factors. The 10 significant salt tolerance-related SNPs and the 25 candidate genes identified in the current study will be a valuable resource for molecular marker development and marker-assisted selection for breeding lettuce varieties with improved salt tolerance at the seed germination stage.

The NHR-23-regulated putative protease inhibitor mlt-11 gene is necessary for C. elegans cuticle structure and function.

C. elegans molting offers a powerful entry point to understanding developmentally programmed apical extracellular matrix remodeling. However, the gene regulatory network controlling this process remains poorly understood. Focusing on targets of NHR-23, a key transcription factor that drives molting, we confirmed the Kunitz family protease inhibitor gene mlt-11 as an NHR-23 target. Through reporter assays, we identified NHR-23-binding sites that are necessary and sufficient for epithelial expression. We generated a translational fusion and demonstrated that MLT-11 is localized to the cuticle and lined openings to the exterior (vulva, rectum, mouth). We created a set of strains expressing varied levels of MLT-11 by deleting endogenous cis-regulatory element sequences. Combined deletion of two cis-regulatory elements caused developmental delay, motility defects, and failure of the cuticle barrier. Inactivation of mlt-11 by RNAi produced even more pronounced defects. mlt-11 is necessary to pattern every layer of the adult cuticle, suggesting a broad patterning role prior to the formation of the mature cuticle. Together these studies provide an entry point into understanding how individual cis-regulatory elements function to coordinate expression of oscillating genes involved in molting and how MLT-11 ensures proper cuticle assembly.