Search Results (70,745)

Foot rot is a major infectious cause of lameness in dairy cows and can severely compromise production performance and animal welfare. However, it remains unclear whether foot rot is accompanied by microbiota alterations beyond the hoof, particularly in the vagina and milk. We conducted a case–control study of 24 Holstein cows (12 with clinical foot rot and 12 healthy controls). Hoof swabs, milk, and vaginal swabs were collected and analyzed using 16S rRNA gene amplicon sequencing, alongside quantitative PCR. Microbial community composition differed between cows with foot rot and healthy controls across hoof (R² = 0.26), vaginal (R² = 0.072), and milk (R² = 0.16) samples (Bray–Curtis, PERMANOVA, p < 0.001). Simpson diversity was lower in the hoof and vaginal microbiota (p < 0.05) but not in milk (p = 0.13). Differential abundance analysis identified enrichment of Fusobacterium in hoof and vaginal samples (p < 0.001), and absolute qPCR confirmed a higher vaginal load of Fusobacterium necrophorum in cows with foot rot (p < 0.05). Milk samples from foot rot cows showed enrichment of Clostridium and Porphyromonas. Co-occurrence network analysis revealed reduced microbial connectivity in foot rot-affected cows (average degree: 4.98 vs. 6.70) and increased network fragmentation (14 vs. 9 modules), suggesting lower ecosystem stability. Overall, foot rot was associated with microbiota shifts across the hoof, vagina, and milk, highlighting the potential value of integrated management strategies that consider extra-hoof microbial alterations. Full article

Background/Objectives: Wound repair-associated processes and the antioxidant properties of natural products play critical roles in skin wound healing and barrier restoration. Wound healing is a complex process characterized by a series of interconnected events that facilitate the self-repair of the skin following injury. Methods: This study aimed to evaluate the effects of Quercus acuta acorn bran extract (QAABE) on wound healing using human dermal fibroblast (HDF) cell cultures treated with QAABE. Additionally, in vivo experiments were conducted using a mouse model of skin injury to assess the wound-healing potential of the extract. Results: The results indicated that QAABE enhanced wound healing in vitro by upregulating extracellular matrix-related markers, including vimentin, Col1a1, Col3a1, endothelin, fibronectin, and VEGF at the mRNA level, and increasing the protein expression of vimentin, COL1A1, endothelin, and α-SMA. QAABE also exhibited reactive oxygen species (ROS)-scavenging activity. In the mouse skin injury model, QAABE treatment accelerated wound closure and was associated with reduced inflammatory responses. Conclusions: These findings suggest that QAABE may promote wound-healing-related responses in both in vitro and in vivo models, supporting its potential as a candidate for further investigation in wound-healing research. Full article

Background/Objectives: This exploratory study (n = 6 per group) investigated the associations between supplementation with α-lipoic acid (AL), betaine (BT), and L-carnitine (LC) and gut microbiota composition in a high-fat diet (HFD)-induced obesity mouse model. Methods: Four-week-old male C57BL/6J mice were fed a control diet (10% fat), HFD (60% fat), or HFD supplemented with AL, BT, or LC (300 mg/kg BW/day) for nine weeks. Results: All three compounds were associated with shifts in microbial composition compared to the HFD-only group. While AL and BT supplementation moderately modulated specific Firmicutes and Bacteroidetes taxa, LC supplementation was linked to a more pronounced reduction in the Firmicutes/Bacteroidetes ratio and a decreased abundance of genera such as Christensenellaceae, Lachnospiraceae, and Coprococcus 3. These microbial changes were correlated with obesity-related metabolic and adiposity markers, including leptin and lipid parameters. Furthermore, functional profiling via PICRUSt suggested potential alterations in amino acid metabolism; however, these findings represent inferred metabolic potential rather than direct metagenomic measurements. Conclusions: Collectively, these results indicate differential associations between dietary supplementation and gut microbiota composition in HFD-fed mice. Although this study was conducted within an exploratory framework and utilized a modest sample size, the observed microbial shifts consistently paralleled metabolic alterations, supporting biologically plausible associations that warrant further mechanistic investigation. Full article

Brucella is a neglected foodborne pathogen, which contaminates milk, dairy products, meat, and meat products of infected animals. However, the role of the Brucella putative effector (BPE) protein family, which relies on the type IV secretion system (T4SS) in Brucella abortus, remains unclear. We demonstrated that BPE159 mediates the regulation of host nuclei in autophagy. The host-interacting protein Eci1 was screened using yeast two-hybridization, molecular docking, and immunoprecipitation, and BPE159-deleted (ΔBPE159) and complementary (ΔBPE159-C) strains were constructed by homologous recombination. We evaluated their growth, survival, and replication and measured the expression of autophagy-related cytokine mRNAs in macrophages. BPE159 was localized in the nucleus of host cells and interacted with Eci1 to downregulate the expression of macrophage autophagy factors, thereby inhibiting host autophagy and enabling the persistence of Brucella. These findings highlight the critical role of BPE159 in mediating autophagy through Eci1 in host cells to promote Brucella survival in host cells. Full article

Aux/IAA proteins function as central transcriptional repressors in auxin signaling and have been implicated in coordinating developmental responses to environmental stress, particularly through modulation of root system architecture. However, the contribution of auxin signaling components to drought-associated root plasticity in improving drought resilience in potato (Solanum tuberosum L.) remains unclear. In this study, we profiled Aux/IAA responses to water deficit across underground tissues by RNA sequencing of root tips, stolon tips, and tubers from two cultivars (Qingshu 9 and Atlantic) with contrasting drought tolerance. Drought treatment induced broad transcriptional changes in the Aux/IAA family, with the majority of members showing increased expression in at least one tissue. qRT-PCR across tissues and developmental stages validated distinct spatiotemporal patterns for selected candidates. Among these, the StIAA3, StIAA6, StIAA22, and StIAA25 genes displayed drought-inducible expression, whereas StIAA24 showed an opposite trend. To probe functional relevance, we generated overexpression and knockdown lines for StIAA3, StIAA6, StIAA22, and StIAA24. Altered expression of these genes was consistently associated with measurable changes in root architecture traits, including root length, diameter, and volume, under water-deficit conditions. These findings reveal insights into the contribution of auxin signaling components to drought-associated root plasticity in potato. The identified drought-responsive Aux/IAA candidates that link root architectural remodeling provide a foundation for mechanistic dissection and underground tissue remodeling of architecture enhancement in root crops. Full article

Background/Objectives: Acute myeloid leukemia (AML) remains a hematologic malignancy with poor prognosis. The neddylation inhibitor MLN4924 has demonstrated potent anti-leukemic activity in preclinical models, yet its clinical translation faces significant challenges. The aim of this study was to explore combination therapy strategies that could further enhance MLN4924’s anti-leukemia potential. Methods: AML cell lines used in this study were Kasumi-1 and MOLM-13. Cell viability was assessed using CCK-8 assays. mRNA and protein expression levels were determined through RT-qPCR and Western blot, respectively. Flow cytometry was employed to analyze surface markers (SLC1A5, CD11b, CD14, CD16), mitochondrial membrane potential (JC-1), and apoptosis (Annexin V-FITC/PI). In vivo efficacy was validated using an NCG mouse xenograft model. Transcriptomic profiling was performed to explore the potential mechanism by which MLN4924 in combination with V9302 inhibits leukemia. Results: Treatment with MLN4924 significantly upregulated key glutamine metabolic proteins, GLUL and the glutamine transporter SLC1A5, in AML cells. Knockdown of SLC1A5 significantly enhanced AML cell sensitivity to MLN4924. The combination of MLN4924 and the SLC1A5 inhibitor V9302 synergistically inhibited AML cell proliferation, induced monocytic differentiation, and promoted apoptosis. Transcriptomic analysis revealed that this combination therapy prominently suppressed the tricarboxylic acid (TCA) cycle. Conclusions: Neddylation inhibition induces compensatory upregulation of glutamine metabolism in AML. Co-targeting neddylation and glutamine transporter SLC1A5 synergistically exerts anti-leukemic effects, at least in part through disruption of the TCA cycle. This combination represents a novel and effective therapeutic strategy against AML. Full article

Successful organ regeneration depends on coordinated cell-to-cell communication mediated by ligand–receptor interactions that regulate proliferation, differentiation, and axonal guidance. Sea cucumbers, particularly Holothuria glaberrima, exhibit remarkable regenerative capacity following evisceration, regenerating their complete intestinal system within weeks. To identify molecular signals orchestrating these events, we characterized five ligand–receptor groups of axonal guidance molecules (Netrin/UNC5-DSCAM, Ephrin/Eph receptors, Semaphorin/Plexin, RGMα/Neogenin, and SLIT/ROBO) using transcriptomic databases from regenerating intestines and the radial nerve cord. Comparative analyses confirmed these as highly conserved orthologs, retaining characteristic structural domains essential for guidance signaling. Multiple alternatively spliced isoforms were detected, with tissue-specific variants suggesting functional diversification. Differential gene expression analysis across intestinal regeneration stages (12 hours to 21 days post-evisceration) revealed distinct temporal patterns: Netrin-1 showed significant upregulation at 7–14 days post-evisceration, coinciding with nerve fiber invasion into the intestinal anlage, while the Ephrin, Semaphorin, and SLIT–ROBO pathways exhibited late-stage expression associated with luminal tissue formation. Single-cell RNA sequencing from 9-dpe regenerating intestines localized Netrin to coelomic epithelial cells and UNC5B to differentiating epithelial cells, with CellChat analysis predicting strong epithelial-to-epithelial signaling. These findings strongly suggest that axonal guidance molecules play dual roles during intestinal regeneration: directing neural innervation in early-to-mid stages and orchestrating tissue boundary formation at later stages. Full article

Background: The integration of multi-omics data, such as genomics and transcriptomics, into artificial intelligence models has advanced precision medicine. However, their clinical applicability remains limited due to model complexity. We integrated DNA mutation, RNA expression, and A>I(G) RNA editing data to develop a predictive model for drug response in breast cancer. Methods: We analyzed 104 patients from the Breast Cancer Genome-Guided Therapy Study (ClinicalTrials.gov: NCT02022202). Clinical variables, gene expression, tumor and germline DNA variants, and RNA editing features were integrated into machine learning models to predict therapy response. Generalized linear models (GLM), random forest (RF), and support vector machines (SVM) were trained and evaluated across multiple random 70/30 train-test splits. Feature selection was performed exclusively within the training set using LASSO regularization. Model performance was assessed using the F1-score on independent test sets. The additive effect of RNA editing was evaluated using paired comparisons across identical train/test splits. Results: We characterized the cohort using clinical, mutational, transcriptomic, and RNA editing profiles in 69 non-responders and 35 responders. Across repeated splits, adding RNA editing frequently maintained or modestly improved predictive performance, particularly in expression-based models, with paired analyses showing a statistically significant increase in F1-score. Conclusions: RNA editing represents a complementary molecular layer that can enhance multi-omic models for therapy response prediction in breast cancer, supporting further investigation of epitranscriptomic features in precision oncology. Full article

Background: High-energy diets enriched in simple sugars and saturated fatty acids alter metabolic homeostasis, yet how distinct nutrients are integrated at the transcriptional level remains incompletely understood. Methods: Here, we profiled the larval midgut transcriptome of Drosophila melanogaster following 24 h exposure to diets enriched with 5% fructose (FD), 1% palmitic acid (PD), or their combination (MD). RNA sequencing (Illumina NovaSeq) was performed on pooled third-instar larval midguts, and differential expression analyses were conducted to identify diet-associated transcriptional changes. Results: The results revealed extensive transcriptional remodeling, with most responses being diet-specific, alongside a conserved core of genes regulated across all treatments. Shared transcriptional signatures were associated with proteostasis and amino acid transport pathways. Comparative and pattern-based analyses further uncovered discordant gene sets and pathway enrichments that were unique to individual diets or to the combined exposure. Notably, the mixed diet induced distinct expression patterns with specific functional signatures that were not predictable from either nutrient alone. Conclusions: Together, these findings indicate that the larval midgut integrates carbohydrate and lipid inputs through coordinated and context-dependent transcriptional responses, highlighting the importance of nutrient combinations in shaping epithelial metabolic programs. Full article

Drought stress is a significant environmental factor affecting plant growth, fruit quality and distribution. Wild jujube is an important species of eco-economic forest tree. In this study, two wild jujube families, ‘NO. 1’ (tolerant) and ‘NO. 5’ (sensitive), which show significant differences in morphological and physiological indicators in drought treatment, are considered. Compared with the ‘NO. 5’, the ‘NO. 1’ exhibited lower water loss, leaf yellowing and abscission rates, as well as reduced malondialdehyde (MDA) content, while showing higher superoxide dismutase (SOD) activity and elevated levels of soluble sugars (SS), soluble proteins (SP), and proline (Pro). In contrast, the ‘NO. 5’ suffered more severe damage to leaf epidermal cells compared with the ‘NO. 1’, accompanied by a significant decline in net photosynthetic rate (A) and instantaneous water use efficiency (WUEi). Transcriptomic profiles between two wild jujube families with markedly different drought responses (withholding water for 15 days) are shown. The two wild jujube families included 3238 up-regulated and 2675 down-regulated differentially expressed genes (DEGs). Many DEGs enriched in the GO and KEGG pathways are related to antioxidant activity, transmembrane transport, carbohydrate biosynthesis and metabolism, plant hormones, and photosynthesis. The biosynthesis of amino acids, the MAPK signaling pathway, plant hormone signal transduction, and flavonoid and alkaloid biosynthesis were the transcriptome modifications most significantly altered by drought stress. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify the precision of the RNA-seq data. ZjJIP23-1, ZjbZIP53, ZjSPS8, ZjCAO, ZjADH1 and ZjERF39 may play important roles in the drought tolerance of the wild jujube. This study provides a solid foundation for further studies on the complex mechanisms and breeding of drought-resistant plants in wild jujube. Full article

Impatiens hawkeri W. Bull (I. hawkeri) is popular among consumers due to its diverse flower colors and year-round blooming. However, changes in ecological conditions, cultivation methods, and planting scale have led to increased disease incidence and diversity, particularly the widespread and destructive leaf spot disease. Currently, studies addressing the pathogen species and its biological characteristics remain limited. In this study, a highly pathogenic strain (IH-4) was selected from previously isolated fungi associated with leaf spot in I. hawkeri. Its taxonomic status was confirmed using upright fluorescence microscope analysis, internal transcribed spacer (ITS)/large subunit (LSU)/RNA polymerase II second largest subunit (rpb2)/β-tubulin (tub2) rRNA gene sequencing, and phylogenetic tree construction. Additionally, the biological characteristics of the pathogen and its sensitivity to 8 chemical fungicides were assessed. Strain IH-4 was identified as Ectophoma multirostrata (E. multirostrata) through combined morphological and molecular approaches. Optimal growth conditions included a temperature of 25 °C, a pH of 7, Potato Dextrose Agar (PDA) medium, fructose as the optimal carbon source, and urea as the optimal nitrogen source, with the fastest growth observed under a semi-light photoperiod (12 h light/12 h dark). Fungicide sensitivity assays indicated that 25% azoxystrobin exhibited the lowest half-maximal effective concentration (EC₅₀, 0.0724 μg/mL) and the steepest virulence regression slope (1.7), demonstrating the strongest inhibitory activity and highest sensitivity. Microscopic observations revealed that IH-4 hyphae penetrate I. hawkeri leaf tissues via stomata, colonize internally, and consequently cause host damage. This study provides a theoretical foundation for the timely and effective management of leaf spot disease in I. hawkeri. Full article

Sepsis is characterized by dysregulated immune responses induced by damage-associated molecular patterns, such as extracellular cold-inducible RNA-binding protein (eCIRP), that frequently lead to acute lung injury (ALI) and high mortality. Recently, a subset of CD4⁺ T cells possessing both T helper 1 (Th1) and regulatory T cell (Treg) phenotypes, termed Th1-Treg cells, has been identified; however, their function in sepsis remains unknown. In this study, we investigated the dynamics, induction mechanisms, and functional roles of Th1-Treg cells in the development of sepsis-induced ALI. Polymicrobial sepsis was induced in mice using cecal ligation and puncture. In vivo, Th1-Treg cell accumulation in the lungs was analyzed in WT and CIRP^−/− mice following sepsis. In vitro, isolated CD4⁺ T cells from WT and TLR4^−/− mice were treated with eCIRP to evaluate Th1-Treg cell differentiation and downstream signaling pathways. STAT1 and STAT5 activation were evaluated, and pharmacological inhibitors were used to assess their involvement. Adoptive transfer of Th1-Treg cells was conducted to determine their functional impact on ALI and mortality in septic mice. We observed a significant accumulation of Th1-Treg cells in the lungs of WT septic mice compared to sham mice. eCIRP drove the induction of Th1-Treg cells in vitro, and CIRP^−/− mice exhibited decreased Th1-Treg cell accumulation in the lungs compared to WT mice after sepsis. In parallel to Th1-Treg cell induction, eCIRP activated signal transducer and activator of transcription, STAT1 and STAT5. Both the induction of Th1-Treg cells and the activation of STAT1/5 proteins were significantly attenuated in TLR4^−/− mice. Furthermore, pharmacological inhibition of STAT1/5 signaling significantly reduced eCIRP-induced Th1-Treg cell differentiation. Intriguingly, adoptive transfer of Th1-Treg cells significantly exacerbated ALI, resulting in increased mortality in sepsis. Our findings indicate Th1-Treg cells induced by the eCIRP–TLR4–STAT1/5 axis aggravate ALI, worsening mortality in sepsis. Targeting these pathogenic cells potentially alleviates sepsis-induced ALI. Full article

Background/Objectives: Floral bud morphogenesis is a critical developmental process determining yield potential in blueberry, yet the molecular regulatory mechanisms in leaves during this phase remain poorly understood. Methods: In this study, we employed a time-series transcriptomic approach to investigate leaf gene expression dynamics during floral bud morphogenesis in rabbiteye blueberry. Leaves were sampled at six time points spanning the critical developmental window from the cessation of summer shoot growth to bud swell and dormancy onset. Results: RNA-seq analysis generated 121.68 Gb of clean data, and weighted gene co-expression network analysis (WGCNA) identified four stage-specific modules (brown, red, blue, turquoise) significantly associated with distinct morphogenetic phases. The brown module (0–6W) was enriched in photosynthesis and hormone signaling pathways, while the red (9W) and blue (12W) modules featured protein processing, stress and hormone signaling, and carbohydrate metabolism. The turquoise module (15W) was dominated by carbon metabolism and flavonoid biosynthesis genes. Key flowering-related genes exhibited dynamic expression patterns: FT was specifically upregulated at the late stage (15W), AP2 genes peaked at mid-stage (9–12W), and COL9 showed early high expression (0–3W). Hormone-related gene analysis revealed extensive involvement of multiple pathways, with brassinosteroid (BR) signaling comprising the largest number of genes (101). Co-expression networks further identified hub genes, including FT, COL9, AP2, ERF1, SR160, LOX3-1, and transcription factor genes like MYB-related, as potential central regulators. Conclusions: Our findings demonstrate that blueberry leaves undergo a phased functional transition from a photosynthetic source to a hub for signal integration and metabolic support during floral bud morphogenesis, actively contributing to reproductive development through systemic signaling. This study provides novel insights into flowering regulation in woody perennials and establishes a foundation for marker-assisted breeding and cropping season management in blueberry. Full article

Termite guts represent a unique microbial habitat harboring bacteria with potential probiotic properties, owing to their ability to inhibit pathogenic microorganisms. This study investigated the probiotic characteristics of lactic acid bacteria newly isolated from the guts of the termite Termes propinquus, aiming to enhance growth performance and reduce the incidence of foodborne pathogen contamination in the commonly consumed edible two-spotted crickets (Gryllus bimaculatus). In this study, five morphologically different bacteria (TPL-1 to TPL-5) were isolated and respectively identified as Levilactobacillus brevis, Lactiplantibacillus plantarum, Streptococcus anginosus, Companilactobacillus alimentarius, and Aerococcus viridans based on 16S rRNA gene sequences and MALDI-TOF MS. All isolates were evaluated for tolerance to stressful conditions (pH 2.5 and 0.3% bile salts), cell surface properties, antioxidant activity, antimicrobial activity against foodborne pathogens, safety profiles, and adhesion to human colon adenocarcinoma cells (Caco-2 and HT-29). Among them, Lactiplantibacillus plantarum TPL-2 demonstrated the strongest probiotic attributes and was further assessed for anti-adhesion activity against foodborne pathogens and in vivo effects on the crickets. Dietary supplementation with Lb. plantarum TPL-2 significantly improved cricket growth, survival, and gut microbiota homeostasis. These findings point to the prospect of termite-derived lactic acid bacteria as beneficial probiotics for use in biotechnological applications and edible insect farming. Full article

Plum pox virus (PPV) is one of the most destructive pathogens affecting stone fruit trees. It causes sharka disease and severe yield losses. The genetically modified plum cultivar ‘HoneySweet’ was developed to provide long-lasting resistance to PPV via RNA interference. Long-term field trials of ‘HoneySweet’ have been conducted in the Czech Republic since 2001, involving the artificial inoculation of the cultivar with PPV alone, and with apple chlorotic leaf spot virus (ACLSV) and prune dwarf virus (PDV) in combination. This study evaluates the impact of viral infection on tree growth after 24 years in the field. Growth parameters—trunk cross-sectional area (TCSA) and canopy volume—were measured and analysed using ANOVA and Tukey’s test. The results show that infected trees exhibit significantly reduced growth compared to non-infected controls, with the strongest inhibition observed in trees inoculated with PPV + PDV + ACLSV. The presence of ACLSV had the most pronounced negative effect on growth, while PDV did not significantly influence tree vigour. These findings emphasise the importance of using virus-free rootstocks and certified planting material to prevent growth suppression in HoneySweet orchards. Full article