Search Results (26,103)

Sprouty-related proteins with enabled/vasodilator-stimulated phosphoprotein homology 1 (EVH1) domain (SPREDs) are negative regulators of the Ras/MAPK signaling pathway and are known to modulate developmental and endocrine processes. While the roles of SPRED1 and SPRED2 are increasingly understood, the physiological relevance of SPRED3 remains elusive. To elucidate its function, we generated SPRED3 knockout (KO) mice and performed phenotypic, molecular, and hormonal analyses. SPRED3-deficient mice exhibited growth retardation and a non-Mendelian genotype distribution. X-Gal staining revealed Spred3 promoter activity in the thyroid, adrenal gland, pituitary, cerebral cortex, and kidney. Hormonal profiling identified elevated thyroid-stimulating hormone (TSH) and reduced thyroxine (T₄) levels, indicating primary hypothyroidism. Thyroidal extracellular signal-regulated kinase (ERK) signaling was mildly reduced in SPRED3 KO mice, and immunoblotting revealed altered expression of autophagy regulators, including reduced sequestosome 1 (p62), increased autophagy-related gene 5 (ATG5), as well as an elevated microtubule-associated protein 1 light chain 3 (LC3) II/I ratio and a decreased pBeclin/Beclin ratio in SPRED3 KO mice. Our findings indicate that SPRED3 is involved in thyroidal homeostasis and plays a regulatory role in autophagy processes within the thyroid gland. Full article

Group A rotavirus (RVA) is a leading causative agent of diarrhea in both young animals and humans. In China, multiple genotypes are commonly found within the bovine population. In this study, we investigated 1917 fecal samples from calves with diarrhea between 2022 and 2025, with 695 testing positive for RVA, yielding an overall detection rate of 36.25%. The highest positivity rate was observed in Hohhot (38.98%), and annual detection rates ranged from 26.75% in 2022 to 42.22% in 2025. A bovine rotavirus (BRV) strain, designated 0205HG, was successfully isolated from a fecal sample of a newborn calf. Its presence was confirmed through cytopathic effects (CPEs), the indirect immunofluorescence assay (IFA), electron microscopy (EM), and high-throughput sequencing. Genomic characterization identified the strain as having the G6-P[¹]-I2-R2-C2-M2-A3-N2-T6-E2-H3 genotype constellation. The structural proteins VP2 and VP7, along with nonstructural genes NSP1–NSP4, shared high sequence identity with Chinese bovine strains, whereas VP1, VP4, and NSP5 clustered more closely with human rotaviruses, and VP3 was related to feline strains. These findings highlight the genetic diversity and interspecies reassortment of BRVs in China, underlining the importance of continued surveillance and evolutionary analysis. Full article

Glucosinolates are secondary metabolites of the Brassicales, playing a role in plant protection and as health-promoting compounds. Here, Na₂SO₄ was used to modulate the aliphatic glucosinolate content in different organs of Eruca sativa Mill. In flowers, which accumulate the highest amount of glucosinolates, Na₂SO₄ increased the concentration of glucoraphanin, in roots of glucoerucin and in apical leaves it doubled the amount of dimeric 4-mercaptobutyl glucosinolate. The biosynthetic gene Branched-Chain Aminotransferase 4 was also induced in roots at the highest salt concentration, while in leaves all tested genes biosynthetic genes were downregulated or unaffected. Cytochromes P450 83A1 monooxygenase was downregulated at the highest salt concentration in all organs. Overall, E. sativa is a reliable source of glucosinolates, which can be modulated with Na₂SO₄. Full article

The development of bioactive materials in endodontics has advanced tissue regeneration by enhancing the biological responses of periradicular tissues. Recently, calcium silicate-based sealers have gained attention for their superior biological properties, including biocompatibility, osteoconductivity, and cementogenic potential. This study aimed to evaluate the cytotoxicity, biocompatibility, and bioactivity of EndoSequence BC Sealer (ES BC) and AH Plus Bioceramic Sealer (AHP BC) using human periodontal ligament stromal cells (hPDLSCs). Biocompatibility was assessed using MTT, Live/Dead, and wound healing assays. ES BC and AHP BC demonstrated significantly higher cell viability and proliferation compared to AH Plus used as a control. Gene expression analysis via real-time quantitative PCR demonstrated that ES BC, especially in set form, significantly upregulated osteogenic markers—alkaline phosphatase (2.49 ± 0.10, p < 0.01), runt-related transcription factor 2 (2.33 ± 0.13), and collagen type I alpha 1 chain (2.85 ± 0.40, p < 0.001)—more than cementogenic markers (cementum protein 1, cementum attachment protein, and cementum protein 23). This differential response may reflect the fibroblast-dominant nature of hPDLSCs, which contain limited cementoblast-like cells. This study supports the superior biocompatibility and regenerative capacity of ES BC and AHP BC compared to AH Plus. While in vitro models provide foundational insights, advanced ex vivo approaches are crucial for translating findings to clinical practice. Full article

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired mucociliary clearance due to defects in motile cilia. This study investigates the impact of loss-of-function mutations in the CFAP300 gene on the ciliary structure and function in three PCD patients. Using a multimodal approach, we integrated molecular genetic testing, transmission electron microscopy, the high-speed video microscopy assay and immunofluorescence staining to analyze ciliary motility and protein expression in both ex vivo and in vitro-obtained ciliary cells. Our results revealed that the pathogenic variant c.198_200delinsCC (p.Phe67ProfsTer10) in CFAP300 led to the absence of the functional CFAP300 protein, the complete loss of outer and inner dynein arms and immotile cilia. Air–liquid interface (ALI)-cultured cells from patients exhibited no ciliary beating, contrasting with healthy controls. Immunostaining confirmed the absence of CFAP300 in patient-derived cilia, underscoring its critical role in dynein arm assembly. These findings highlight the diagnostic utility of ALI cultures combined with functional and protein analyses for PCD, offering a clinically actionable framework that can be readily incorporated into standard diagnostic workflows. Full article

To investigate the responses and mechanisms of slash pine under low orthophosphate (Pi) stress and to identify Pi-efficient lines, we analyzed 12 indices related to biomass, root traits, and tissue Pi concentration across 13 slash pine lines subjected to varying Pi treatments. The composite assessment value of low-phosphorus tolerance (D) was calculated by evaluating these 12 response indicators through principal component analysis, in conjunction with the fuzzy membership function method. Nine low-phosphorus tolerance factors (LPTFs)—including above-ground fresh weight (0.69), below-ground fresh weight (0.52), total root length (0.56), root surface area (0.63), root volume (0.67), above-ground Pi concentration (0.78), below-ground Pi concentration (0.52), bioconcentration factor (0.77), and P utilization efficiency (−0.76)—showed significant correlations with D (p < 0.05). Utilizing these nine LPTFs, cluster analysis classified the 13 lines into the following three groups according to their low-phosphorus (P) tolerance: high-P-efficient, medium-P-efficient, and low-P-efficient lines. Under low Pi and Pi-deficiency treatments, line 27 was identified as a high-P-efficient line, while lines 1, 6, and 9 were classified as low-P-efficient lines. Notably, eight genes (SPX1, SPX3, SPX4, PHT1;1, PAP23, SQD1, SQD2, NPC4) and five genes (SPX1, SPX3, SPX4, PAP23, SQD1) were significantly up-regulated in the roots and leaves of both line 27 and line 9 under low-phosphorus stress, respectively. However, the high-P-efficient line 27 exhibited a stronger regulatory capacity with a higher expression of two genes (SPX4, SQD2) in the roots and nine genes (SPX1, SPX3, SPX4, PHT1;1, PAP10, PAP23, SQD1, SQD2, NPC4) in the leaves under low Pi stress. These findings reveal differential responses to low Pi stress among slash pine lines, with line 27 displaying superior low-P tolerance, enabling better adaptation to low Pi environments and the maintenance of normal growth, development, and physiological activities. Full article

Blue mold of pome fruit, caused by Penicillium expansum, is controlled through postharvest applications of thiabendazole (TBZ), pyrimethanil (PYR), and fludioxonil (FDL). However, multi-fungicide-resistant isolates have emerged in the U.S. Pacific Northwest and their impact on decay control in long-term storage is unknown. This study evaluated the fitness of P. expansum isolates sensitive to all three postharvest fungicides (wild-types) and those resistant to TBZ (single-resistant), TBZ and PYR, or PYR and FDL (dual-resistant), and triple-resistant to the three fungicides. On nutrient-poor media, resistant isolates showed reduced conidial germination, whereas no significant differences were observed in germination, mycelial growth, or sporulation between phenotypes on nutrient-rich media at 1.5 and 20 °C. Regardless of their sensitivity phenotype, FDL-resistant isolates showed increased sensitivity to osmotic and oxidative stresses. Pathogenicity and virulence were not affected by the sensitivity phenotype on apples after six months of storage at 1.5 °C. Analysis of cumulative fitness changes indicated fitness loss under low-temperature in vitro and increased fitness under fungicide selection pressure on fruit in most resistant phenotypes. Gene expression analysis showed differential regulation of fitness-related genes, with most being up-regulated by TBZ. Overall, the results suggest that resistance in P. expansum may carry context-dependent fitness penalties, especially under high-stress conditions. Full article

Tooth development (odontogenesis) is regulated by interactions between epithelial and mesenchymal tissues through signaling pathways such as Bone Morphogenetic Protein (BMP), Wingless-related integration site (Wnt), Sonic Hedgehog (SHH), and Fibroblast Growth Factor (FGF). Mesenchymal stem cells (MSCs) derived from dental tissues—including dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and dental follicle progenitor cells (DFPCs)—show promise for regenerative dentistry due to their multilineage differentiation potential. Epigenetic regulation, particularly DNA methylation, is hypothesized to underpin their distinct regenerative capacities. This study reanalyzed publicly available DNA methylation data generated with Illumina Infinium HumanMethylation450 BeadChip arrays (450K arrays) from DPSCs, PDLSCs, and DFPCs. High-confidence CpG sites were selected based on detection p-values, probe variance, and genomic annotation. Principal Component Analysis (PCA) and hierarchical clustering identified distinct methylation profiles. Functional enrichment analyses highlighted biological processes and pathways associated with specific methylation clusters. Noncoding RNA analysis was integrated to construct regulatory networks linking DNA methylation patterns with key developmental genes. Distinct epigenetic signatures were identified for DPSCs, PDLSCs, and DFPCs, characterized by differential methylation across specific genomic contexts. Functional enrichment revealed pathways involved in odontogenesis, osteogenesis, and neurodevelopment. Network analysis identified central regulatory nodes—including genes, such as PAX6, FOXC2, NR2F2, SALL1, BMP7, and JAG1—highlighting their roles in tooth development. Several noncoding RNAs were also identified, sharing promoter methylation patterns with developmental genes and being implicated in regulatory networks associated with stem cell differentiation and tissue-specific function. Altogether, DNA methylation profiling revealed that distinct epigenetic landscapes underlie the developmental identity and differentiation potential of dental-derived mesenchymal stem cells. This integrative analysis highlights the relevance of noncoding RNAs and regulatory networks, suggesting novel biomarkers and potential therapeutic targets in regenerative dentistry and orthodontics. Full article

While a global downward trend in rotavirus diarrhea cases has been observed following vaccine introduction, reassortment, genetic drift, and vaccine-escaping strains remain a concern, particularly in Sub-Saharan Africa. Here, we provide genomic insights into three equine-like G3P[8] rotavirus strains detected in Benin during the post-vaccine era. Whole-genome sequencing was performed using the Illumina MiSeq platform, and genomic analysis was conducted using bioinformatics tools. The G3 of the study strains clustered within the recently described lineage IX, alongside the human-derived equine-like strain D388. The P[8] is grouped within the lineage III, along with cognate strains from the GenBank database. Both the structural and non-structural gene segments of these study strains exhibited genetic diversity, highlighting the ongoing evolution of circulating strains. Notably, we identified a novel NSP2 lineage, designated NSP2-lineage VI. Amino acid comparisons of the G3 gene showed two conservative substitutions at positions 156 (A156V) and 260 (I260V) and one radical substitution at position 250 (K250E) relative to the prototype equine-like strain D388, the equine strain Erv105, and other non-equine-like strains. In the P[8] gene, three conservative (N195G, N195D, N113D) and one radical (D133N) substitutions were observed when compared with vaccine strains Rotarix and RotaTeq. These findings suggest continuous viral evolution, potentially driven by vaccine pressure. Ongoing genomic surveillance is essential to monitor genotype shifts as part of the efforts to evaluate the impact of emerging strains and to assess vaccine effectiveness in Sub-Saharan Africa. Full article

Background: Merkel cell polyomavirus (MCPyV) has been established as an etiological agent in Merkel cell carcinoma (MCC), yet its role in other cutaneous neoplasms remains under investigation. The impact of the host’s immunogenetic characteristics on the persistence of Merkel cell polyomavirus (MCPyV) in non-melanoma skin cancer (NMSC) is not yet well understood. Objective: Our aim was to investigate the presence of MCPyV in various skin lesions, particularly NMSC, and its association with cytokine gene polymorphisms related to immune regulation. Methods: We analyzed 274 skin biopsies (lesional, perilesional, and healthy skin) from 84 patients undergoing dermatological evaluation. MCPyV DNA and polymorphisms in IL-6, IL-10, IFN-γ, and TNF-α genes were detected using PCR-based assays. Results: MCPyV was significantly more prevalent in NMSC and non-cancerous lesions than in surgical margins or healthy skin (p = 0.050 and 0.048, respectively). Concordance between lesion and margin samples was low (κ = 0.305), suggesting microenvironment-specific viral persistence. Notably, high-expression IL-10 genotypes (-1082 GG) and low-expression IL-6 genotypes (-174 AA) were significantly associated with MCPyV detection (p = 0.048 and p = 0.015, respectively). Conclusions: MCPyV preferentially localizes to NMSC lesions, particularly in individuals with immunogenetic profiles favoring viral persistence. Since the role of MCPyV in the pathogenesis of NMSC remains uncertain, our results highlight the need for further studies to clarify whether the lesion’s microenvironment supports viral persistence or indicates a more intricate interaction between the virus and the host, which could be significant for the development of skin cancer. Full article

This study aimed to assess whether dietary supplementation with probiotics could alleviate intestinal injury in lipopolysaccharide (LPS)-challenged piglets. Healthy weaned piglets were randomly allocated to four individual groups (n = 6): (1) a control group; (2) an LPS group; (3) an LPS + Lactobacillus group; and (4) an LPS + Bacillus group. The control and LPS groups received a basal diet, while the probiotic groups were provided with the same basal diet supplemented with 6 × 10⁶ cfu/g of Lactobacillus casei (L. casei) or a combination of Bacillus subtilis (B. subtilis) and Bacillus licheniformis (B. licheniformis) at a dosage of 3 × 10⁶ cfu/g, respectively. On day 31 of the trial, overnight-fasted piglets were killed following the administration of either LPS or 0.9% NaCl solution. Blood samples and intestinal tissues were obtained for further analysis several hours later. The results indicate that dietary supplementation with probiotics significantly exhibited health-promoting effects compared with the control group and effectively reduced LPS-induced histomorphological damage to the small intestine, impairments in barrier function, and dysregulated immune responses via modulation of enzyme activity and the expression of relevant genes, such as nuclear factor-kappa B (NF-κB), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), claudin-1, nuclear-associatedantigenki-67 (Ki-67), and β-defensins-1 (pBD-1). Collectively, these results suggest that dietary supplementation with probiotics could alleviate LPS-induced intestinal injury by enhancing the immunity and anti-inflammatory responses in piglets. Our research provides a theoretical basis for the rational application of probiotics in the future. Full article

The rugose surface trait in pepper (Capsicum annuum L.), marked by ridges and depressions on the fruit epidermis, is linked to improved fruit texture. To investigate its regulatory basis, histological, textural, and transcriptomic differences, contrasting genotypes were analyzed. Histological analysis revealed that disorganized epidermal cell layers contribute to rugosity, with morphological differences emerging around 10 days post-anthesis (DPA). A computer-aided design (CAD)-based rugosity index (RI) was developed and showed strong correlation with sensory rugosity scores (R² = 0.659, p < 0.001). Texture analysis demonstrated that increasing surface rugosity was associated with reduced rupture force and hardness, as well as elevated pectinase activity. Comparative transcriptome profiling identified 10 differentially expressed genes (DEGs) related to microtubule dynamics (e.g., CA03g18310 and CA09g13510) and phytohormone signaling (e.g., CA03g35180 and CA08g12070), which exhibited distinct spatial and temporal expression patterns. These findings suggest that coordinated cytoskeletal remodeling and hormonal regulation drive epidermal disorganization, leading to surface rugosity and altered fruit texture. The study provides novel insights into the molecular basis of fruit surface morphology and identifies promising targets for breeding high-quality pepper cultivars. Full article

Gut microbiota plays a vital role in host resilience but may be disrupted under environmental antibiotic pressure. The goitered gazelle (Gazella subgutturosa), a keystone ungulate in the Qaidam Basin, is crucial for ecosystem stability. We aimed to investigate how this species responds to antibiotic pressure through gut microbial adaptation. Using 16S rRNA sequencing and weighted gene co-expression network analysis (WGCNA) on fecal and soil samples from six regions, we identified 18 microbial modules, of which three were strongly associated with antibiotics (|r| ≥ 0.75, p < 0.05). Gut microbial α-diversity was lowest in the antibiotic-rich, vegetation-poor TGL region and highest in XRH, where diverse vegetation appeared to buffer antibiotic impact. Antibiotic pressure can reshape gut microbial communities, exerting both adaptive benefits and adverse effects. High-quality habitats may alleviate the negative impacts of antibiotic pressure. Full article

Mycoplasmal pneumonia of sheep (MPS), caused by Mesomycoplasma (Mycoplasma) ovipneumoniae, profoundly impacts ovine productivity and survival. Although gut–lung microbiota interactions are increasingly recognized in respiratory diseases, whether similar crosstalk occurs between the lung and rumen microbiota in MPS-affected sheep remains unknown. To investigate alterations in the lung and rumen microbiota of sheep with MPS, the crosstalk between these microbial communities, and their impacts on growth phenotypes. From a cohort of 414 naturally infected six-month-old male Hu sheep, we selected 10 individuals with severe pulmonary pathology and 10 healthy controls for detailed phenotypic and microbiome analyses. Assessment of 359 phenotypic traits revealed that MPS significantly impairs feed efficiency and growth rate (p < 0.05). Through 16S rRNA gene sequencing, we found that MPS significantly altered the pulmonary microbiota community structure (p < 0.01), with a noticeable impact on the rumen microbiota composition (p = 0.059). Succinivibrionaceae_UCG-001 was significantly depleted in both the rumen and lungs of diseased sheep (p < 0.05) and strongly associated with reduced average daily feed intake (p < 0.05). In addition, pulmonary Pasteurella and ruminal Succinivibrionaceae_UCG-002 were significantly enriched in MPS-affected sheep, showed a strong positive correlation (p < 0.05), and were both negatively associated with feed efficiency (p < 0.05). Notably, Pasteurella multocida subsp. gallicida may act as a keystone species influencing feed efficiency. These findings point to a previously unrecognized rumen-lung microbial axis that may modulate host productivity in sheep affected by MPS. This work provides new insights into the pathogenesis of MPS and offers potential targets for therapeutic intervention and management. Full article

Heavy metal pollution, particularly copper contamination, threatens the ecological environment and human survival. In response to this pressing environmental issue, the development of innovative remediation strategies has become imperative. Bioremediation technology is characterized by remarkable advantages, including its ecological friendliness, cost-effectiveness, and operational efficiency. In our previous research, Rossellomorea sp. ZC255 demonstrated substantial potential for environmental bioremediation applications. This study investigated the removal characteristics and underlying mechanism of strain ZC255 and revealed that the maximum removal capacity was 253.4 mg/g biomass under the optimal conditions (pH 7.0, 28 °C, and 2% inoculum). The assessment of the biosorption process followed pseudo-second-order kinetics, while the adsorption isotherm may fit well with both the Langmuir and Freundlich models. Cell surface alterations on the Cu(II)-treated biomass were observed through scanning electron microscopy (SEM). Cu(II) binding functional groups were determined via Fourier transform infrared spectroscopy (FTIR) analysis. Simultaneously, the genomic analysis of strain ZC255 identified multiple genes potentially involved in heavy metal resistance, transport, and metabolic processes. These studies highlight the significance of strain ZC255 in the context of environmental heavy metal bioremediation research and provide a basis for using strain ZC255 as a copper removal biosorbent. Full article