Search Results (122,236)

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

Excess caloric intake and insufficient physical activity are the two major drivers underlying the global obesity and type 2 diabetes mellitus epidemics. However, circadian misalignment of caloric intake and physical activity, as commonly experienced by nightshift workers, can also have detrimental effects on body weight and glucose homeostasis. We have previously reported that combined restriction of eating and voluntary wheel running to the inactive phase (i.e., a rat model for circadian misalignment) shifted liver and muscle clock rhythms by ~12 h and prevented the reduction in the amplitude of the muscle clock oscillation otherwise induced by light-phase feeding. Here, we extended on these findings and investigated how a high-fat diet (HFD) affects body composition and liver and muscle clock gene rhythms in male Wistar rats while restricting both eating and exercise to either the inactive or active phase. To do this, we used four experimental conditions: sedentary controls with no wheel access on a non-obesogenic diet (NR), sedentary controls with no wheel access on an HFD (NR-H), and two experimental groups on an HFD with simultaneous access to a running wheel and HFD time-restricted to either the light phase (light-run-light-fed + HFD, LRLF-H) or the dark phase (dark-run-dark-fed + HFD. DRDF-H). Consumption of an HFD did not alter the daily running distance of the time-restricted groups but did increase the running intensity in the LRLF-H group compared to a previously published LRLF chow fed group. However, no such increase was observed for the DRDF-H group. LRLF-H ameliorated light phase-induced disturbances in the soleus clock more effectively than under chow conditions and had a protective effect against HFD-induced changes in liver clock gene expression. Together with (our) previously published results, these data suggest that eating healthy and being active at the wrong time of the day can be as detrimental as eating unhealthy and being active at the right time of the day. Full article

The Mycoplasmataceae are a family of bacteria that typically cause respiratory, arthritic, and genitourinary disease in humans. Mycoplasma spp. of animal origin are also the causative agents of porcine wheezing disease, chronic respiratory disease and arthritis in chickens and other conditions. These diseases have a significant impact on public health and the economic development of livestock breeding. Clinical prevention and treatment of mycoplasma infections is primarily dependent on the use of antibiotics. However, inappropriate and excessive use of antimicrobials has enabled resistance development that has become a significant clinical concern. Mycoplasma are also robust biofilm producers, and this process is a major factor for the persistence of these infections, especially in conjunction with common antibiotic resistance mechanisms, including target gene mutations and the action of efflux pumps. A mycoplasma biofilm refers to a structured and stable microbial community formed by Mycoplasma spp. adhering to biological or non-biological surfaces under suitable conditions and secreting extracellular polymers (EPS) such as polysaccharides. This process allows the microorganisms to adapt to their surrounding environment and survive during the growth process. These biofilms render bacteria more resistant to antimicrobials than planktonic bacteria, resulting in biofilm-associated infections that are more challenging to eradicate and more likely to recur. The current study reviews progress from the fields of biofilm formation, structure and identification, correlations between biofilms and drug resistance and virulence as well as methods of biofilm prevention and control. Our aim was to provide a reference basis for the subsequent in-depth understanding of the research of mycoplasma biofilms. Full article

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. 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

In this study, GH19 chitinase (Chi) gene family was systematically identified and characterized using genomic assemblies from four cotton species: Gossypium barbadense, G. hirsutum, G. arboreum, and G. raimondii. A suite of analyses was performed, including genome-wide gene identification, physicochemical property characterization of the encoded proteins, subcellular localization prediction, phylogenetic reconstruction, chromosomal mapping, promoter cis-element analysis, and comprehensive expression profiling using transcriptomic data and qRT-PCR (including tissue-specific expression, hormone treatments, and Fusarium oxysporum infection assays). A total of 107 GH19 genes were identified across the four species (35 in G. barbadense, 37 in G. hirsutum, 19 in G. arboreum, and 16 in G. raimondii). The molecular weights of GH19 proteins ranged from 9.9 to 97.3 kDa, and they were predominantly predicted to localize to the extracellular space. Phylogenetic analysis revealed three well-conserved clades within this family. In tetraploid cotton, GH19 genes were unevenly distributed across 12 chromosomes, often clustering in certain regions, whereas in diploid species, they were confined to five chromosomes. Promoter analysis indicated that GH19 gene promoters contain numerous stress- and hormone-responsive motifs, including those for abscisic acid (ABA), ethylene (ET), and gibberellin (GA), as well as abundant light-responsive elements. The expression patterns of GH19 genes were largely tissue-specific; for instance, GbChi23 was predominantly expressed in the calyx, whereas GbChi19/21/22 were primarily expressed in the roots and stems. Overall, this study provides the first comprehensive genomic and functional characterization of the GH19 family in G. barbadense, laying a foundation for understanding its role in disease resistance mechanisms and aiding in the identification of candidate genes to enhance plant defense against biotic stress. Full article

Extracts, fractions and the pure compound epifriedelanol of the medicinal plant Synadenium glaucescens have antibacterial properties. Herbal products are generally considered less prone to resistance development than conventional antimicrobials, as they contain multiple compounds, which makes bacteria less likely to develop resistance. However, data supporting this notion are lacking. This study evaluated the development of resistance in Staphylococcus aureus subjected to extract, fractions and epifriedelanol of S. glaucescens. It also identified S. aureus fitness genes contributing to intrinsic resistance to extract of S. glaucescens. Fluctuation and gradient concentration assays were used to determine mutation rates and growth adaptation, respectively, which were lower following exposure to growth in crude extract than the pure compound epifriedelanol. By subjecting 1920 single gene mutants from the Nebraska Transposon Mutant Library to growth in the presence of extract of S. glaucescens, 12 genes were identified as important for natural resistance in S. aureus JE2; however, only mutation in the hemB gene decreased the minimum inhibitory concentration by greater than 4-fold (64-fold). In conclusion, purifying active antimicrobial compounds from S. glaucescens and using them as antibacterial substances as an alternative to crude extract increased the risk of resistance development. Further, the gene hemBappears to have a significant role in the natural resistance to the extracts obtained from S. glaucescens in this study. 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

Excessive alcohol consumption is associated with systemic health risks due to the production of acetaldehyde, a primary carcinogen that not only pollutes the environment but also endangers human health. In this study, a promising bacterial strain for biodegrading both ethanol and acetaldehyde was successfully isolated from the traditional fermented food Jiaosu and identified as Acetobacter ghanensis JN01 based on average nucleotide identity (ANI) analysis. Initial ethanol of 1 g/L was completely biodegraded within 4 h, while initial acetaldehyde of 1 g/L was also rapidly removed at 2 or 1 h by whole cells or cell-free extracts (CEs) of JN01, respectively, which indicated that JN01 indeed has a strong ability in the biodegradation of both ethanol and acetaldehyde. Whole-genome sequencing revealed a 2.85 Mb draft genome of JN01 with 57.0% guanine–cytosine (GC) content and the key metabolic genes (adh1, adh2, and aldh) encoding involving alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), co-located with NADH dehydrogenase genes and ethanol-responsive regulatory motifs, supporting the metabolic pathway of transforming ethanol to acetaldehyde, and, subsequently, converting acetaldehyde to acetic acid. Furthermore, selected in vitro safety-related traits of JN01 were also assessed, which is very important in the development of microbial catalysts against both ethanol and acetaldehyde. Full article

Speed is not only the primary objective of racehorse breeding but also a crucial indicator for evaluating racehorse performance. This study investigates a newly developed racehorse breed in China. Through whole-genome resequencing, we selected 60 offspring obtained from the crossbreeding of Thoroughbred horses and Xilingol horses for this study. This breed is tentatively named “Grassland-Thoroughbred”, and the samples were divided into two groups based on racing ability: 30 racehorses and 30 non-racehorses. Based on whole-genome sequencing data, the study achieved an average sequencing depth of 25.63×. The analysis revealed strong selection pressure on chromosomes (Chr) 1 and 3. Selection signals were detected using methods such as the nucleotide diversity ratio (π ratio), integrated haplotype score (iHS), fixation index (Fst), and cross-population extended haplotype homozygosity (XP-EHH). Regions ranked in the top 5% by at least three methods were designated as candidate regions. This approach detected 215 candidate genes. Additionally, the Fst method was employed to detect Indels, and the top 1% regions detected were considered candidate regions, covering 661 candidate genes. Functional enrichment analysis of the candidate genes suggests that pathways related to immune regulation, neural signal transmission, muscle contraction, and energy metabolism may significantly influence differences in performance. Among these identified genes, PPARGC1A, FOXO1, SGCD, FOXP2, PRKG1, SLC25A15, CKMT2, and TRAP1 play crucial roles in muscle function, metabolism, sensory perception, and neurobiology, indicating their key significance in shaping racehorse phenotypes. This study not only enhances understanding of the molecular mechanisms underlying racehorse speed but also provides essential theoretical and practical references for the molecular breeding of Grassland-Thoroughbreds. Full article

Renal oncocytoma (RO) is a benign renal neoplasm characterized by dense accumulation of dysfunctional mitochondria possibly resulting from increased mitochondrial biogenesis and decreased mitophagy; however, the mechanisms controlling these mitochondrial changes are unclear. ROs harbor recurrent inactivating mutations in mitochondrial genes encoding the Electron Transport Chain (ETC) Complex I, and we hypothesize that Complex I loss in ROs directly impairs mitophagy. Our analysis of ROs and normal kidney (NK) tissues shows that a significant portion (8 out of 17) of ROs have mtDNA Complex I loss-of-function mutations with high variant allele frequency (>50%). ROs indeed exhibit reduced Complex I expression and activity. Analysis of the various steps of mitophagy pathway demonstrates that AMPK activation in ROs leads to induction of mitochondrial biogenesis, autophagy, and formation of autophagosomes. However, the subsequent steps involving lysosome biogenesis and function are defective, resulting in an overall inhibition of mitophagy. Inhibiting Complex I in a normal kidney cell line recapitulated the observed lysosomal and mitophagy defects. Our data suggest Complex I loss in RO results in defective mitophagy due to lysosomal loss and dysfunction. Full article

Arsenic (As) contamination has significantly increased in recent decades due to anthropogenic activities. This is a serious challenge for human health, environmental quality, and crop productivity. Biochar (BC) is an important practice used globally to remediate polluted soils. Likewise, melatonin (MT) has also shown tremendous results in mitigating metal toxicity and improving crop productivity. Nevertheless, the mechanism of combined BC and MT in alleviating As toxicity in rice (Oryza sativa L.) remains unexplored. In this study, we investigated how As affected rice and how the combined BC and MT facilitated As tolerance. The study comprised a control, As stress (100 mg kg⁻¹), As stress (100 mg kg⁻¹) + BC (2%), As stress (100 mg kg⁻¹) + MT (100 µM) and As stress (100 mg kg⁻¹) + BC (2%) + MT (100 µM). Arsenic significantly decreased rice growth and yield by increasing electrolyte leakage (EL), malondialdehyde (MDA), and hydrogen peroxide (H₂O₂). Co-applying BC and MT substantially enhanced rice growth and yield by increasing chlorophyll synthesis (48.12–92.42%) leaf water contents (40%), antioxidant activities (ascorbate peroxide: 56.43%, catalase: 55.14%, peroxidase: 57.77% and superoxide dismutase: 57.52%), proline synthesis (41.35%), MT synthesis (91.53%), and phytochelatins synthesis (125%) nutrient accumulation in rice seedlings and soil nutrient availability. The increased rice yield with BC + MT was also linked with reduced H₂O₂ production, As accumulation, soil As availability, and an increase in OsAPx6, OsCAT, OsPOD, OsSOD OsASMT1, and OsASMT2 and a decrease in expression of OsABCC1. Biochar + MT enhanced residual OM- and Fe, ((Fe₂As) and Mn (Mn₃(AsO₄)₂) bound forms of As leading to a substantial increase in rice growth and yield. Thus, the combination of BC and MT is an eco-friendly approach to mitigate As toxicity and improve rice productivity. 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