Search Results (19,965)

The genomes of viruses in the Allexivirus genus encode the p42 protein, which is considered the hallmark of the genus. The functions of p42 have not yet been studied experimentally and cannot be predicted based on sequence similarity, as p42-related proteins are not found among known cell or viral proteins. Here, p42 of Shallot virus X (ShVX), the type allexivirus, is demonstrated to be translated via a leaky scanning mechanism on a template comprising three “triple gene block” (TGB) transport genes and the p42 gene. Sequence analysis shows that this p42 expression mechanism is conserved in the vast majority of allexiviruses. p42 binds single-stranded RNA (ssRNA) but not double-stranded RNA (dsRNA) in vitro and localizes to the cytoplasm in association with microtubules and microtubule-bound bodies. In transient expression assays, p42 exhibits weak but detectable suppression of silencing induced by ssRNA but not by dsRNA. In addition, p42 suppresses silencing in the context of virus infection. Furthermore, p42 inhibits nonsense-mediated RNA decay (NMD) induced by a long 3′-terminal untranslated region of mRNA. Taken together, these findings provide initial evidence that the ShVX TGB/p42 gene module functions as a single genomic unit in terms of protein expression, that p42 acts as a suppressor of NMD and silencing, and that it may have multiple roles, while the precise biological significance of p42 in these roles remains to be experimentally confirmed. Full article

BRAF inhibitors have a 50–70% response rate in melanoma but are less effective for thyroid cancer. Differential response may be from activation or expression of downstream mitogen-activated protein kinase (MAPK) pathway genes. Retrospective analysis compared whole exome and transcriptome sequencing in melanoma and thyroid cancers from April 2019 to October 2023. The MAPK Activation Score (MPAS) was calculated using Z-score normalized/log-transformed values indicating expression across 10 MAPK-associated genes. Our tumor registry provided outcome data. BRAF V600E mutations were identified in 33 of 200 (17%) melanomas and 14 (7%) had other BRAF mutations (V600K/R). Of 49 thyroid tumor samples, BRAF V600E mutations were found in 19 (39%). RNA expression of BRAF and the 10 MAPK-associated genes were increased in melanomas with V600E compared to wild-type BRAF (p = 0.02). Conversely, BRAF V600E mutation in thyroid cancer was not associated with increased expression nor MAPK pathway activation. No significant difference in overall survival based on BRAF mutation was observed in the subset of patients where data was available. The MAPK pathway is differentially affected by the different cancers, with increased MAPK activation observed in melanoma and not in thyroid cancer. This may account in part for the observed differential response to BRAF inhibitors. Full article

Background: Perinatal research faces significant challenges in understanding placental biology and maternal–fetal interactions due to limited access to human tissues and the lack of reliable models. Emerging technologies, such as liquid biopsy and single-cell analysis, offer novel, non-invasive approaches to investigate these processes. This scoping review explores the current applications of these technologies in placental development and the diagnosis of pregnancy complications, identifying research gaps and providing recommendations for future studies. Methods: This review adhered to PRISMA-ScR guidelines. Studies were selected based on their focus on liquid biopsy or single-cell analysis in perinatal research, particularly related to placental development and pregnancy complications such as preeclampsia, preterm birth, and fetal growth restriction. A systematic search was conducted in PubMed, Scopus, and Web of Science for studies published in the last ten years. Data extraction and thematic synthesis were performed to identify diagnostic applications, monitoring strategies, and biomarker identification. Results: Twelve studies were included, highlighting the transformative potential of liquid biopsy and single-cell analysis in perinatal research. Liquid biopsy technologies, such as cfDNA and cfRNA analysis, provided non-invasive methods for real-time monitoring of placental function and early identification of complications. Extracellular vesicles (EVs) emerged as biomarkers for conditions like preeclampsia. Single-cell RNA sequencing (scRNA-seq) revealed cellular diversity and pathways critical to placental health, offering insights into processes such as vascular remodeling and trophoblast invasion. While promising, challenges such as high costs, technical complexity, and the need for standardization limit their clinical integration. Conclusion: Liquid biopsy and single-cell analysis are revolutionizing perinatal research, offering non-invasive tools to understand and manage complications like preeclampsia. Overcoming challenges in accessibility and standardization will be key to unlocking their potential for personalized care, enabling better outcomes for mothers and children worldwide. Full article

Understanding the genetic basis of high-performance animals is vital for biological insight and breeding. This study aimed to identify genetic factors distinguishing champion gamecocks (Gallus gallus domesticus) from less successful ones, representing the first study to link transcriptomic profiles directly to competitive outcomes. Using RNA sequencing on non-invasive feather samples, we compared gene expression between high-performing (≥80% win rate) and low-performing (≤20% win rate) cohorts. Our analysis identified 441 differentially expressed genes. Notably, the high-performing cocks exhibited the significant upregulation of genes integral to muscle development and repair (e.g., SYNPO2, POPDC2) and enhanced neural function (NRN1). Conversely, several genes involved in neural development pathways, including CNTNAP2 and GFRA4, were significantly downregulated in the high-performing group. These findings suggest that a rooster’s competitive success is not determined by a single factor, but by a complex interplay of superior muscular capabilities and uniquely regulated neurological pathways. The identified genes provide a set of potential biomarkers that could inform selective breeding strategies aimed at enhancing performance traits in gamecocks. Full article

Bartonella spp. is a Gram-negative bacterium transmitted by arthropod vectors, implicated in a range of zoonotic infections affecting both humans and animals. Among zoonotic species, B. henselae is primarily associated with domestic cats and B. vinsonii with dogs. In Italy, Bartonella infections have been reported in both southern and northern regions. This study investigates the presence of Bartonella spp. in fleas and ticks collected from companion animals in Piedmont region, northwestern Italy. A total of 176 flea and 85 tick specimens were obtained from 92 animals (dogs and cats) between May 2018 and February 2020. Arthropods were morphologically identified using identification keys, and screened for Bartonella DNA by PCR targeting the 16s rRNA gene. Positive samples were further analyzed by amplifying the rpoB gene. Selected 16s-positive and all rpoB-positive samples were sequenced and subjected to phylogenetic analysis. Fleas were mostly identified as Ctenocephalides felis, recovered from 44 cats and 12 dogs; a single C. canis specimen was found in one cat. Ticks were Ixodes ricinus (from 14 cats and 10 dogs), Rhipicephalus sanguineus s.l. (3 cats, 7 dogs), and Dermacentor marginatus (one dog). Bartonella prevalence was 38.4%, with 34.2% positivity in fleas and 45.6% in ticks. All sequences corresponded to B. henselae. These findings confirm the active circulation of B. henselae in ectoparasites of pets and raise questions about the potential role of ticks in its transmission. Full article

The plant microbiome plays a role in pathogen defense, but its role in different resistant varieties and ecological niches remains unclear. This study used 16S rRNA and ITS sequencing to investigate microbial communities and interactions in disease-resistant (PT) and susceptible (Bourbon) coffee varieties of five ecological niches: leaves, fruits, roots, rhizosphere soil, and non-rhizosphere soil. We found that the microbial communities differed significantly between the two varieties. The resistant variety was enriched in beneficial bacteria from the Actinobacteriota phylum and a stable, modular microbial network dominated by saprotrophic fungi. In contrast, the susceptible variety had a higher abundance of opportunistic pathogens and stress-indicator fungi, including Neurospora spp., which were more prominent in the rhizosphere and non-rhizosphere soils. These networks were fragile and dominated by pathotrophic fungi, reflecting ecological imbalance. Our findings show that plant disease resistance is influenced not only by host genetics but also by co-evolutionary interactions with the microbiome. These insights provide a foundation for developing targeted biocontrol strategies to manage plant-associated microbial communities. Full article

Hippophae rhamnoides ssp. sinensis Rousi a species of significant ecological and economic value that is native to the Qinghai–Tibet Plateau and arid/semi-arid regions. Investigating the mitochondrial genome can elucidate stress adaptation mechanisms, population genetic structure, and hybrid evolutionary history, offering molecular insights for ecological restoration and species conservation. However, the genetic information and evolutionary mechanisms of its mitochondrial genome remain poorly understood. This study aimed to assemble the complete mitochondrial genome of H. rhamnoides L. ssp. sinensis using Illumina sequencing, uncovering its structural features, evolutionary pressures, and environmental adaptability and addressing the research gap regarding mitochondrial genomes within the Hippophae genus. The study assembled a 454,444 bp circular mitochondrial genome of H. rhamnoides ssp. sinensis, with a GC content of 44.86%. A total of 73 genes and 3 pseudogenes were annotated, with the notable absence of the rps2 gene, which is present in related species. The genome exhibits significant codon usage bias, particularly with high-frequency use of the alanine codon GCU and the isoleucine codon AUU. Additionally, 449 repetitive sequences, potentially driving genome recombination, were identified. Our evolutionary pressure analysis revealed that most genes are under purifying selection, while genes such as atp4 and nad4 exhibit positive selection. A nucleotide diversity analysis revealed that the sdh4 gene exhibits the highest variation, whereas rrn5 is the most conserved. Meanwhile, phylogenetic analysis showed that H. rhamnoides ssp. sinensis from China is most closely related to Hippophae tibetana, with extensive homologous sequences (49.72% of the chloroplast genome) being identified between the chloroplast and mitochondrial genomes, indicating active inter-organellar gene transfer. Furthermore, 539 RNA editing sites, primarily involving hydrophilic-to-hydrophobic amino acid conversions, were predicted, potentially regulating mitochondrial protein function. Our findings establish a foundation for genetic improvement and research on adaptive evolutionary mechanisms in the Hippophae genus, offering a novel case study for plant mitochondrial genome evolution theory. Full article

Objectives: This study aimed to investigate the effects of the quorum-quenching enzyme N-acyl-homoserine lactone (AHL)-lactonase Est816 on biofilm formation in subgingival plaque microbiota from participants with advanced periodontitis. Methods: Subgingival plaque samples were collected from 30 adults with untreated Stage III or higher periodontitis and cultured anaerobically. Est816 was applied in vitro, with phosphate-buffered saline (PBS) serving as the control. Biofilm composition was analyzed via 16S rRNA sequencing, and alpha diversity metrics were assessed. Differential taxa abundance was assessed with the multivariate statistical software MaAsLin3. Biofilm morphology, biomass, and thickness were evaluated using scanning electron microscopy (SEM), crystal violet staining, and confocal laser scanning microscopy (CLSM). Results: Est816 significantly reduced microbial richness (Chao1 Index, p = 0.031), biofilm biomass (64% reduction, p < 0.001), and thickness (76% reduction, p < 0.001) compared to controls. SEM revealed fragmented biofilm architecture in Est816-treated samples. Conclusions: AHL-lactonase Est816 inhibited polymicrobial subgingival-plaque-derived biofilm formation while reducing species richness, phylogenetic diversity, and community evenness. These findings demonstrate Est816’s potential as an adjunctive therapy for disrupting pathogenic biofilms in periodontitis. Full article

This paper reports the first case in which a hyperlipidemic retriever (due to hypothyroidism) with a nasal tumor was successfully treated—achieving partial remission—and managed using a metronomic combination of chlorambucil (3.74 mg/m², SID) and prednisolone (0.28 mg/kg, SID) orally for 9 months at a general practice. A 35 kg spayed female golden retriever aged 8 years and 8 months with nosebleeds visited the Bundang New York Animal Hospital in July 2023 after being diagnosed with nasal carcinoma. A protocol of 4 weeks of chemotherapy followed by 1 week of rest was repeated in two cycles and continued metronomically for 9 months without pause after the two cycles. The nasal exudate was significantly reduced. The size of the nasal tumor was monitored using computed tomography (CT) imaging at a referral hospital. Since the first occurrence of epistaxis, 18 months have passed (as of January 2025) and the nasal exudate is barely visible, and the vital signs and weight of the dog remain stable. The size of the nasal tumor significantly decreased after 9 months of chemotherapy completion without moderate side effects, and all the blood work was normalized, including hypercholesteremia. This study demonstrates that, in hyperlipidemic cancer patients, a prednisolone/chlorambucil metronomic combination which is cost-effective can be an alternative to tyrosine kinase inhibitors such as sorafenib, even when excluding the price. Through a literature review, the author also investigates the effect of the hyperlipidemic state on cancer, focusing on carcinoma and vascular endothelial growth factor (VEGF), as well as the RAS-RAF-MEK pathway, which is a target for tyrosine kinase inhibitors, in order to reveal the molecular mechanism of chlorambucil metronomic chemotherapy. Also, the author investigates the molecular pathway of carcinoma development in human hyperlipidemia patients through single-cell RNA sequence analysis using open public data, and discusses the molecular action of chlorambucil. Full article

Meat quality is influenced by genetic, nutritional, and microbial factors, with increasing attention on the role of gut-derived metabolites. In this study, we conducted untargeted metabolomics of 10 gut tract sites and RNA sequencing (RNA-seq) of longissimus dorsi muscles in Meigu goats and Liangshan black sheep raised under standardized conditions. Results showed that goat muscle contained significantly higher levels of essential amino acids (e.g., methionine) and specific fatty acids (e.g., C18:3_N6, C20:4_N6), suggesting improved nutritional quality. Transcriptomic analysis identified 3133 differentially expressed genes (DEGs), among which ADCY1 and SLC38A4 were upregulated in goats and strongly associated with meat traits. Using integrative correlation analysis, we uncovered 17 genes and 19 gut metabolites that were significantly correlated with more than eight meat quality parameters across multiple gut sites. Notably, these metabolites included bioactive compounds such as L-tyrosine ethyl ester and pelargonidin 3-O-glucoside, while genes were enriched in pathways related to amino acid transport, cAMP signaling, and muscle development. Together, these findings highlight a potential gut–muscle axis involving metabolite-mediated modulation of muscle gene expression, contributing to breed-specific differences in meat composition and quality. This study provides a valuable framework for improving ruminant meat quality through integrative multi-omics analysis. Full article

The colonization of Fusobacterium nucleatum (F. nucleatum) in the microenvironment of gastric cancer (GC) is closely associated with tumor progression, but its impact on host metabolic remodeling remains unclear. This study aims to elucidate the mechanistic link between F. nucleatum infection and metabolic changes in GC tissue. By integrating 16S rRNA microbiome sequencing and LC-MS/MS metabolomics, the differences in microbial composition and metabolic profiles between Fusobacterium sp.-positive and -negative GC tissues were systematically compared, and the correlation of differential microbes and differential metabolites was analyzed. The impact of F. nucleatum on the glutathione (GSH) metabolic pathway was validated through in vitro tissue testing and the use of the infection model of GC cell lines (such as AGS and HGC27). Integrative omics analysis showed a strong negative correlation between Fusobacterium sp. infection and antioxidant metabolite GSH levels in GCs (p < 0.001). Metabolic reprogramming features: Eleven differentially expressed metabolites were identified using LC-MS/MS metabolomics screening (p < 0.05). GSH was significantly depleted in the Fusobacterium sp.-positive group. Experimental validation: At the histological level, the abundance of F. nucleatum in GC tissues was higher than that in the paired adjacent non-cancerous (NC) tissues; at the cellular level, after F. nucleatum infection of GC cells, the intracellular GSH level decreased (p < 0.01), accompanied by a decrease in glutathione synthetase (GSS) mRNA expression and reactive oxygen species (ROS). This study is the first to demonstrate that F. nucleatum suppresses the GSH synthesis pathway, leading to the breakdown of antioxidant capacity and the formation of an oxidative stress microenvironment in GC cells. These findings provide new insights into the metabolic mechanism of F. nucleatum in promoting GC progression and suggest that targeting the F. nucleatum-GSH axis could offer a novel strategy for GC therapeutic intervention. Full article

In order to precisely improve the quality of major tree species in northern China, near-natural differentiated management has been gradually introduced into forestry practice, aiming to optimize forest structure, enhance forest quality, and promote nutrient cycling and water conservation. As an essential element of forest ecosystems, soil microbes contribute to biodiversity preservation and nutrient turnover in soils. This study selected three typical forest types (Quercus acutissima forest, Pinus tabulaeformis forest, and Pinus tabulaeformis × Quercus mixed forest) that have been managed with target trees on Zhongtiao Mountain. Using 16S/ITS rRNA high-throughput sequencing, this study systematically assessed the influences of forest type and soil depth (0–60 cm) on the soil properties and microbial communities. The results showed that the fungal alpha diversity indices were the highest in Pinus tabulaeformis forest, which decreased with soil depth. Actinobacteriota exhibited the greatest relative abundance in mixed forest, whereas Ascomycota predominated in the Pinus tabulaeformis forest. The microbial co-occurrence network exhibited greater complexity compared to the pure forest. Microbial carbon and nitrogen cycling functions showed strong correlation with soil pH and nutrient levels. Symbiotrophs dominated the fungal community, and ectomycorrhizae were significantly abundant in mixed forests. pH is the dominant factor driving changes in microbial communities. In summary, the mixed forest improved soil nutrients, enhanced the complexity of microbial networks, and supported higher ectomycorrhizal abundance. These findings provide practical guidance for improving soil health and stability of forest ecosystems through near-natural management. Full article

2-Amino-14,16-dimethyloctadecan-3-ol (AOD) is commonly found in foods contaminated with Fusarium avenaceum, particularly cereals or fruits, and is structurally related to Fusarium mycotoxins (fumonisins) and mammalian sphingoid bases, especially 1-deoxysphinganine (m18:0); therefore, it might enter systemic circulation and tissues upon dietary intake. Knowledge about what happens when cells are exposed to AOD is limited, but it has been reported to be cytotoxic and to induce vacuolization in HepG2 cells. We also found that AOD is cytotoxic for HepG2 cells, but even at a concentration where cell viability remained above 85% (5 μM), it altered 24 differentially expressed genes based on RNA sequencing-based transcriptomic profiling. Among these genes, 13 were shared with cells treated with m18:0. These overlapping differentially expressed genes were primarily enriched in activated stress response pathways of cells, including the upregulation of specific genes in the hypoxia-inducible factor 1α (HIF-1α) signaling pathway, such as hexokinase 1 (HK1) and egl-9 family hypoxia-inducible factor 3 (EGLN3), the activation of key components in the p53 signaling pathway, and the induction of cellular senescence-associated transcriptional programs involving serpin family E member 1 (SERPINE1). Transcriptional analysis of genes related to sphingolipid metabolism showed that treatment with AOD increased the mRNA expression of ceramide synthase 4 (CerS4), sphingosine-1-phosphate phosphatase 1 (SGPP1), and UDP-glucosylceramide glucosyltransferase (UGCG), while decreasing the expression of dihydroceramide desaturase 1 (DEGS1) and fatty acid desaturase 3 (FADS3), a pattern of gene expression changes that mirrored the alterations observed with m18:0 treatment. Lipidomic analyses revealed that AOD significantly perturbed the sphingolipid composition of HepG2 cells, specifically increasing hexosylceramide content while decreasing ceramide and sphingomyelin levels. Moreover, AOD was found to undergo intracellular metabolism to N-acyl-AODs, perhaps by ceramide synthase(s), since this acylation was inhibited by fumonisin B1 (FB1). These findings demonstrate that AOD or possibly its N-acyl metabolites can alter cellular sphingolipid metabolism and affect the expression of genes involved in cell stress. These new insights call for more studies of the impact of this food contaminant on cells and the implications for human health. Full article

Witches’ broom disease of blue palo verde (Parkinsonia florida) was reported more than sixty years ago. Characteristic symptoms consist of dense clusters of shortened, brittle branches and stunted leaves. The suspect causal agent has been identified as palo verde broom virus (PVBV), genus, Emaravirus, family, Fimoviridae. Here, the first complete PVBV genome sequence was determined, and virus small interfering RNAs (vsiRNAs), primary metabolites, and phytohormone profiles were characterized from infected palo verde leaves, adventitious shoots, flowers, and seeds. Based on pairwise distances, PVBV RNAs 1–4 shared 54–65% nucleotide identity and 19–51% amino acid similarity, respectively, with other emaraviruses, while PVBV RNA 5 shared no sequence homology with any emaravirus. The 21–24-nt virus-derived vsiRNAs, indicative of post-transcriptional gene silencing (PTGS), represented nearly the entire PVBV genome in flowers, leaves, seeds, and adventitious shoots; however, PVBV RNA 3 and RNA 4 were most heavily targeted in all plant parts. Evidence that six major phytohormones were altered in PVBV-infected compared to virus-free trees indicated that emaravirus-infected trees mount classical defense responses to virus infection and/or eriophyid mite infestations. Detection of PVBV RNA genome segments 1–5, accumulation of predominantly 21-nt vsiRNAs, homologous to the PVBV genome and transcripts, and altered levels of phytohormones and metabolites in PVBV-infected trees strongly implicate PVBV as the causal agent of witches’ broom disease. Full article

Glucagon-like peptide 1 (GLP-1), a hormone derived from the proglucagon gene, regulates various physiological processes; however, its impact on pregnancy outcomes remains poorly understood. Assessing the effects of GLP-1 on neonates is vital as GLP-1 is increasingly administered during pregnancy. This study evaluates the effect of GLP-1 exposure on maternal complications and neonatal defects in mice. Pregnant female A/J mice received subcutaneous injections of recombinant GLP-1 (rGLP-1; 1000 nmol/kg) on embryonic day 1 (EP, early pregnancy) or day 15 (E15, late pregnancy). Maternal and neonatal body weights, morphology, and mortality were recorded, and mRNA sequencing was conducted to analyze gene expression in neonatal tissues. Maternal body weight decreased following rGLP-1 exposure, and pups born to both the early and late exposure groups experienced significant weight loss. Pups in the late exposure group exhibited uniform skin detachment and a dramatically higher mortality rate than those born to the early exposure group. Further, RT-PCR analysis confirms the significantly increased expression of selected genes in the skin and associated pathogenesis. RNA sequencing of pups’ skin, brain, lung, and liver tissues from the late exposure group showed altered gene expression. Since maternal weight loss, increased neonatal mortality, and altered gene expression have been observed, GLP-1 receptor agonists (GLP-1RAs) should be avoided during pregnancy. Full article