Search Results (36,797)

The ovaries are crucial reproductive organs that regulate the menstrual cycle and support pregnancy through the production of steroid hormones. They are highly susceptible to various environmental pollutants, which can lead to ovarian disorders. Luteal phase defect (LPD) and premature ovarian failure (POF) are common ovarian disorders in women. In this study, we integrate network toxicology with molecular docking and molecular dynamics simulations to elucidate the toxicological mechanisms of Benzo(a)pyrene (BaP), a widespread endocrine disruptor, in LPD and POF. Through systematic data mining of the GeneCards and OMIM databases, we identified 1336 targets associated with LPD and 2066 targets related to POF, as well as 220 BaP targets. Venn diagram analysis revealed 36 potential targets for BaP-induced LPD and 43 for BaP-induced POF. GO and KEGG enrichment analyses suggest that BaP-induced LPD and POF may share toxicological mechanisms. PPI network visualization indicated that EGFR, ESR1, and STAT3 are critical common targets for BaP-induced LPD and POF. Molecular docking and molecular dynamics simulations revealed that BaP exhibits strong binding affinity with all three core genes. In KGN cells modeling LPD and POF phenotypes, cellular experiments confirmed that BaP downregulated EGFR and ESR1 expression while upregulating STAT3 expression, thereby supporting the reliability of these targets in BaP-induced ovarian dysfunction. These findings provide insights into BaP-induced reproductive toxicity and offer a foundation for targeted clinical interventions to mitigate the effects of environmental pollutants on women’s reproductive health. Full article

Background/Objectives: Factors modulating phenotypic variability in Rett syndrome (RTT, OMIM 312750) include X chromosome inactivation (XCI), type of MECP2 variant, and/or disease modifiers. Emerging evidence also points to multi-locus genetic variants. Understanding the phenotypic variability associated with multi-locus genetic diagnoses in individuals with RTT and MECP2-related disorders would be important not only for accurate diagnosis, risk stratification and clinical management but also to explain symptoms that might not be typically associated with RTT. Methods: We present a case series of five individuals with a diagnosis of RTT or an MECP2-related disorder with co-occurring genetic findings, including pathogenic variants, variants of unknown significance and chromosome duplications. Clinical features such as neurodevelopmental history and comorbid medical conditions were assessed alongside the genetic findings. Results: A review of 200 cases with RTT identified five cases (all females aged 7–27 years) with a co-occurring genetic finding. Each case harboured at least one additional genetic variant that included a beta thalassaemia trait, Calmodulin 3 (CALM3) missense variant, maternally inherited 22q12.3 to q13.1 duplication, 7p14.3 and Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) variants of uncertain significance and a pathogenic Set Domain-containing protein 5 (SETD5) variant. A rare triple genetic finding was illustrated in a single case, combining MECP2, CALM3, and DYNC1H1 variants. Conclusions: This case series supports the premise that RTT and MECP2-related disorders exist in a more complex neurogenetic spectrum than previously defined. It also emphasises the complexity within MECP2-related disorders. They are not static, and in the context of severe treatment resistant epilepsy, MECP2 disorders can evolve over time, necessitating diagnostic reclassification. Although the co-occurrence of multiple genetic disorders in RTT and MECP2-related disorders is rare, these cases underscore the importance of considering cumulative genetic burden when evaluating individuals with atypical features or evolving neurodevelopmental phenotypes. Full article

Stickler syndrome is a monogenic connective tissue disorder primarily caused by pathogenic variants in collagen-related genes, most commonly COL2A1. Prenatal diagnosis remains challenging, particularly in healthcare systems with limited access to molecular genetic testing. We report a prenatal case of suspected craniofacial anomaly detected on second-trimester ultrasound. Fetal DNA obtained by amniocentesis underwent next-generation sequencing. Parental testing was performed to assess inheritance. It was confirmed that autosomal dominant Stickler syndrome type I (ORPHA:90653) was caused by a heterozygous pathogenic frameshift variant in COL2A1 (c.3137del) that was inherited from the mother and identified in the fetus. Micrognathia was identified during prenatal ultrasound, and postnatal evaluation revealed characteristics that were consistent with Pierre Robin sequence and connective tissue involvement. The molecular discoveries elucidated the observed phenotype and facilitated multidisciplinary perinatal management. This case underscores the indispensable function of molecular diagnostics in the prenatal identification of monogenic disorders, including Stickler syndrome, in cases where conventional karyotyping is inadequate. Targeted clinical surveillance and family counseling are facilitated by early genetic confirmation. The report also emphasizes the necessity of incorporating molecular diagnostics into routine prenatal care for rare genetic diseases and the systemic limitations in access to genomic testing. Although the identified variant has been previously reported, this case highlights the clinical and diagnostic value of prenatal molecular confirmation in a resource-limited healthcare setting. Full article

Morchella is a nutritious and artificially cultivable rare ascomycete, and its growth and development regulation mechanisms are a current research hotspot. High-temperature stress severely limits the annual yield of Morchella, and this challenge is intensifying with global warming. However, previous studies have lacked systematic screening for heat-tolerant Morchella strains, and their molecular response mechanisms to heat stress remain unclear. In this study, we conducted a comprehensive analysis of phenotypic characteristics, physiological metabolism, and transcriptomics on 19 Morchella strains under normal (25 °C) and high-temperature (30 °C) conditions. The heat-tolerant strain HLM exhibited superior performance in mycelial growth, morphology, and field cultivation. It maintained cell homeostasis under heat stress through mild osmotic regulation (elevated levels of proline, soluble sugars, and proteins), a robust antioxidant system (increased activities of CAT, POD, and SOD), and reduced malondialdehyde accumulation. Transcriptomic analysis identified a novel regulatory model of “stress perception—metabolic preparation—terminal detoxification” in the heat-tolerant strain HLM under heat stress. The rapid upregulation of the SMPD1 gene may mediate ceramide signal generation, promoting G6PDH expression to drive carbon flow into the pentose phosphate pathway, thereby increasing NADPH output. As the detoxification terminal, AKR4C uses this reducing power to eliminate toxic carbonyl end products like malondialdehyde, completing the defense loop. These findings offer new insights into the heat-tolerance mechanisms of large ascomycetes, provide a theoretical foundation for stress-resistant Morchella breeding and cultivation in high-temperature areas, and serve as valuable resources for exploring heat-tolerance mechanisms and molecular breeding in other edible fungi. Full article

Insecticide resistance in Aedes aegypti (Linnaeus, 1762) poses a major challenge for vector control programs, undermining the effectiveness of chemical tools to mitigate both nuisance biting and the transmission of vector-borne diseases. Previous studies have documented widespread resistance to multiple adulticide active ingredients across Florida, particularly pyrethroids, along with high prevalence of knockdown resistance (kdr) mutations. Continued resistance monitoring is essential for guiding treatment decisions and detecting shifts in susceptibility over time. In collaboration with mosquito control programs across Florida, we assessed the susceptibility of 78 Ae. aegypti populations to up to six active ingredients, conducting 396 independent CDC bottle bioassays and calculating hazard ratios relative to a susceptible Ae. aegypti strain. For pyrethroids, 24 h post-exposure mortality was used to evaluate phenotypic recovery from knockdown. Hazard ratios revealed Ae. aegypti populations were more susceptible to organophosphate adulticide active ingredients, while the lowest hazard ratios, indicating higher resistance, were observed for sumithrin, deltamethrin, etofenprox, and permethrin, respectively. Evidence of knockdown resistance and recovery after 24 h was present across all pyrethroid exposures, with the highest levels following treatment with etofenprox and sumithrin. These findings confirm that pyrethroid resistance remains a significant barrier to Ae. aegypti control and provide updated, operationally relevant resistance data that can complement existing guidance and support evidence-based vector management strategies. Full article

Biostimulants can promote healthy plant growth under reduced fertilization and abiotic stress. This study investigated how the efficacy of three commercial biostimulants was influenced by initial substrate pH and fertilizer rate. Biostimulants included Micromate (humic and fulvic acids), Cease (Bacillus subtilis QST 713), and Lalrise Vita (Bacillus velezensis). Petunia × hybrida (petunia) ‘Picobella Blue’ was grown in a peat-based soilless substrate with an initial pH of 5.5, 6.2, or 7.0 and fertilized with either 50 mg·L⁻¹ N (low rate) or 150 mg·L⁻¹ N (recommended rate). Growth and plant health were assessed at flowering using digital phenotyping. The effect of biostimulants on plant growth depended on initial substrate pH and fertilization rate, whereas the vegetation indices were influenced only by fertilization rate. Lalrise Vita increased plant size across all substrate pH levels and fertilizer rates, while improving canopy health indices across fertilization rates. Micromate resulted in the greatest increases in growth, flowering, and canopy health across all pH and fertilizer treatments, with especially strong responses under recommended fertility. Our findings demonstrate that biostimulant efficacy in petunia ‘Picobella Blue’ is context-dependent, varying with product, substrate pH, and fertility rate, demonstrating the need for species- and environment-specific evaluations before widespread greenhouse adoption. Full article

Passiflora germplasm represents an important genetic resource for improving fruit yield and quality in breeding programs targeting semi-arid environments. This study aimed to assess the phenotypic diversity, genetic parameters, and breeding potential of Passiflora accessions conserved in the Passion Fruit Active Germplasm Bank of Embrapa Semiárido. A total of 55 accessions, predominantly Passiflora cincinnata Mast., were evaluated using morphoagronomic descriptors related to plant, flower, and fruit traits. Quantitative data were analyzed using mixed linear models (REML/BLUP) to estimate genetic parameters, and multivariate analyses were applied to characterize phenotypic divergence. Substantial phenotypic variability was observed, particularly for fruit-related traits. Fruit weight ranged from 43.25 to 142.88 g, pulp weight ranged from 7.86 to 51.37 g, and pulp yield ranged from 17.06% to 40.27% among accessions. Broad-sense heritability estimates for key fruit traits were moderate to high, reaching 0.50 for fruit weight, 0.49 for pulp weight, and 0.36 for pulp yield, indicating favorable prospects for selection. Principal Component Analysis explained 66.0% of the total variation in the first two components, with fruit size, pulp-related traits, and seed number contributing most strongly to accession differentiation. Multivariate analyses consistently identified accessions 1 and 16 as superior for fruit weight and pulp yield, whereas accession 55 combined high fruit weight with elevated soluble solid content (up to 14.24 °Brix) but lower pulp yield. Overall, the observed variability highlights the relevance of Passiflora germplasm conserved under semi-arid conditions as a valuable resource for breeding programs focused on fruit yield, quality, and adaptation to water-limited environments. Full article

Background: Sarcopenia is highly prevalent in older adults and in individuals with impaired kidney function, where it is associated with adverse clinical outcomes. A creatinine–cystatin C–based sarcopenic index has been proposed as a surrogate marker of muscle status; however, its association with sarcopenia as defined by the EWGSOP2 framework, particularly in the context of renal dysfunction, remains uncertain. Methods: Older adults were classified according to EWGSOP2 criteria into probable, confirmed, and severe sarcopenia. Associations between the sarcopenic index and sarcopenia phenotypes were examined using group comparisons and multivariable logistic regression analyses in the overall cohort and in a subgroup of participants with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m². Results: The sarcopenic index was not independently associated with probable, confirmed, or severe sarcopenia. In contrast, age emerged as the strongest independent correlate of probable sarcopenia (OR 1.12; 95% CI 1.05–1.19, p = 0.001), while body mass index was independently associated with confirmed sarcopenia (OR 0.91; 95% CI 0.86–0.96, p < 0.001). Similar patterns were observed in participants with reduced kidney function. Conclusions: Within the present analytical framework, the sarcopenic index did not show a meaningful association with EWGSOP2-defined probable sarcopenia, the most uniformly assessable EWGSOP2 stage, in older adults, including those with reduced kidney function. Exploratory analyses of more advanced sarcopenia stages did not reveal additional associative information. These findings should be interpreted within a descriptive and associative framework rather than a formal assessment of diagnostic or clinical decision-making performance. Full article

Conventional echocardiography traditionally relies on population-derived reference values and dichotomous classification schemes that do not fully account for individual patient characteristics or disease complexity. Artificial intelligence (AI) is driving a paradigm shift toward precision echocardiography by enabling patient-specific cardiovascular assessment through the integration of phenotypic, clinical, and biological data. This review examines how AI is transforming echocardiography from a population-based test into a patient-specific assessment tool that supports precision cardiovascular care. It highlights three clinical applications with potential clinical impact: Heart Failure with Preserved Ejection Fraction phenogrouping for targeted therapy selection, cardio-oncology surveillance with individualized cardiotoxicity risk prediction, and cardiomyopathy risk stratification for personalized sudden cardiac death prevention. For each application, it describes the clinical challenge, the AI-enabled precision solution, and its potential clinical impact. It also outlines a practical roadmap for clinical adoption. Precision echocardiography, powered by AI, holds promise for transforming cardiovascular imaging and diagnostics by enabling more patient-specific assessment, earlier disease detection, and personalized therapeutic strategies. Full article

Babesia divergens, a zoonotic tick-borne pathogen, causes bovine and human babesiosis in Europe. The Elongation Factor 1 alpha (EF-1α) protein is important in many cellular processes and has emerged as a possible target for subunit vaccine development against parasitic infections, and its intergenic region (IG) is an important tool for genetic manipulation of Babesia parasites. While the EF-1α locus of B. divergens has been described, structural variation between isolates was poorly defined. In order to fill this gap, we performed a comparative analysis of the EF-1α-IG in B. divergens human (Rouen 87 and Spanish sample) and bovine (Türkiye) host isolates. Our findings revealed both conserved and variable elements, particularly in TA nucleotide repeat numbers and IG sequence length. The Spanish isolate exhibited the highest TA repeat expansion, whereas the Rouen 87 strain had the shortest IG. Given the known role of repeat-rich promoter elements in gene regulation, these differences may influence EF-1α transcription. Additionally, these findings provide insights into the evolutionary divergence of B. divergens and its host adaptation mechanisms. This study establishes a foundation for future gene editing and transfection strategies, where selecting intergenic sequences with varying TA repeats could optimize transfection efficiency and explain phenotypic differences between isolates from different hosts or regions. Full article

Research on biomarkers reflecting tumor biology and systemic metabolism is crucial for improving the accuracy and personalization of breast cancer (BC) prognosis. We investigated circulating dodecanoic acid in 229 patients undergoing radiotherapy (RT) and assessed its association with progression-free survival and overall survival over six years. Patients were classified into two phenotypes based on post-RT changes in dodecanoic acid: The Increase Phenotype (IP) had lower baseline concentrations and showed a post-RT rise, whereas the Decrease Phenotype (DP) had higher pre-RT levels and declined after treatment. Dodecanoic acid levels were lower in tumors than in peritumoral samples, and their association with phenotypes varied by sampling region, suggesting that systemic changes reflect broader metabolic adaptations rather than local tissue concentrations. Post-RT increases in dodecanoic acid were associated with higher paraoxonase-1 activity, suggesting a link with antioxidant status. Patients in the IP group had a significantly lower risk of progression than those in the DP group, whereas no significant differences in overall survival were observed. These findings highlight the potential utility of dodecanoic acid measurement as a prognostic biomarker and suggest that modulating fatty acid metabolism could be explored as a therapeutic strategy. Full article

Crohn’s disease (CD) is characterized by chronic intestinal inflammation accompanied by gut dysbiosis and redox imbalance. We investigated the role of dual oxidase-2 (DUOX2), a major epithelial source of reactive oxygen species (ROS), in linking oxidative stress to microbe–host crosstalk. DUOX2 expression was upregulated in human intestinal samples and was positively associated with inflammatory readouts, oxidative stress indices, and dysbiosis. Intestinal epithelial cell-specific Duox2 knockout (KO) mice exhibited reduced mucosal ROS, preserved barrier integrity, and attenuated dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Cohousing and fecal microbiota transplantation demonstrated that this protective phenotype was microbiota-dependent. Multi-omics profiling identified enrichment of Parabacteroides, particularly P. distasonis, in Duox2 KO mice, and oral supplementation with P. distasonis enhanced resistance to colitis. Mechanistically, DUOX2-derived oxidative stress constrained Parabacteroides growth, as P. distasonis displayed marked susceptibility to hydrogen peroxide, with excessive intracellular ROS accumulation and an absence of key antioxidant defenses—including peroxide reductase C (AhpC) and superoxide dismutase B (SodB)—indicating that epithelial DUOX2 shapes a hostile luminal redox niche unfavorable to these beneficial microbes. Pharmacological inhibition of DUOX2 with Compound 521 reduced oxidative stress, ameliorated colitis, and partially restored microbial balance. These findings establish a DUOX2–ROS–microbiota axis in which epithelial DUOX2 amplifies oxidative stress, remodels the gut ecosystem, and promotes inflammation, and highlights DUOX2 suppression or ROS-sensitive Parabacteroides as potential redox-centric therapeutic strategies for CD. Full article

Gibberellins (GAs) play a crucial regulatory role in the growth and development of cotton (Gossypium hirsutum L.). Through bioinformatics analyses, we identified a total of 39 GA2ox genes (encoding gibberellin 2-oxidases) in the cotton genome, designated GhGA2ox1 to GhGA2ox39. Based on phylogenetic analysis, these genes were classified into five groups. We further examined their gene structures, conserved motifs, and chromosomal distributions, revealing that members within the same group shared similar structural and motif organizations. Collinearity and cis-element analyses provided important insights into the evolutionary history and regulatory potential of the GA2ox gene family in cotton. Notably, using nucleotide diversity (π) and population differentiation (F_ST) analyses across the entire family, we screened and identified nine candidate genes that underwent strong artificial selection during cotton domestication and improvement. Further haplotype-phenotype association analysis identified GH_D09G0919 (GhGA2ox31) as a key regulator of Plant Height (PH). To validate their regulatory roles, we analyzed the genotype distribution in accessions with extreme phenotypes. The results revealed divergent selection histories for these two loci: the favorable allele of GH_D01G0720 (GhGA2ox23) was already fixed in the tested population, whereas GH_D09G0919 maintained significant natural variation. Specifically, the Hap2 allele of GH_D09G0919 was significantly enriched in the shortest accessions compared to the tallest ones. Importantly, quantitative real-time polymerase chain reaction (qRT-PCR) analysis confirmed that the Hap2 allele drives significantly higher gene expression in leaves, suggesting that enhanced GA catabolism underlies the compact phenotype. Additionally, transcriptomic profiling revealed the tissue-specific expression patterns of candidate genes, implying their functional roles in development. Furthermore, functional validation using the Arabidopsis mutant of the homologous gene (AtGA2ox8) confirmed its conserved role in regulating plant height, as the mutant exhibited a distinct short-stature phenotype. These results uncover valuable genetic resources for molecular breeding to shape compact cotton architecture. Collectively, this study aims to analyze the evolutionary patterns of the cotton GA2ox gene family and to identify key genes that regulate plant height under artificial selection, providing theoretical support for molecular breeding of compact plant types. Full article

Objectives: This study aimed to evaluate the genetic and clinical characteristics of hereditary pancreatitis (HP) in a cohort of Romanian pediatric patients, with a focus on the correlation between specific gene mutations and disease severity, recurrence patterns, and associated complications. Methods: A retrospective analysis was conducted on pediatric patients diagnosed with HP. Genetic testing was performed to identify mutations in key genes. Clinical data were collected regarding age of onset, recurrence, severity, surgical interventions, and progression to chronic pancreatitis. Exploratory computational analyses were performed to illustrate potential patterns between genetic variants and clinical characteristics. Results: PRSS1 variants were associated with earlier onset and more severe disease. A substantial proportion of patients developed chronic pancreatitis during the study period. Surgical complications were observed in over half of the cohort. The findings are consistent with the role of genetic mutations in influencing the clinical trajectory of HP. Genotype–phenotype correlations may inform hypotheses regarding early risk stratification and tailored management strategies. Conclusions: Genetic testing is essential for the accurate diagnosis and personalized treatment of HP. Integrating genetic diagnostics into clinical practice may improve outcomes and guide early intervention in high-risk pediatric patients. Full article

Background/Objectives: Immune-mediated hepatitis, including autoimmune hepatitis, remains a formidable clinical challenge characterized by the rapid destruction of the liver parenchyma. While whey proteins are well-regarded for their anti-inflammatory properties, goat whey possesses a distinct bioactive profile, offering superior digestibility and reduced allergenicity compared to their bovine counterparts. This study investigated the hepatoprotective potential and underlying immunological mechanisms of lyophilized goat whey (LGW) in a Concanavalin A (ConA)-induced model of acute hepatitis. Methods: BALB/c and C57BL/6 mice were administered LGW orally (1 g/kg/day) for five consecutive days prior to a ConA challenge. Liver injury was quantified via serum transaminase levels and histopathological evaluation. The cytokine profiles and the phenotype of liver mononuclear cells (MNCs) were analyzed using ELISA and flow cytometry, respectively. Results: LGW pretreatment significantly attenuated ConA-induced hepatitis in both mouse strains, markedly reducing serum transaminase levels and preserving hepatic architecture. Mechanistically, LGW triggered a fundamental shift in the hepatic immune microenvironment by suppressing the pro-inflammatory Th1/Th17 axis (evidenced by decreased IFN-γ and IL-17) while concurrently upregulating the anti-inflammatory cytokine IL-10. Furthermore, LGW induced a tolerogenic phenotype in hepatic dendritic cells (CD11c⁺CD206⁺), which directly correlated with a significant expansion of regulatory T cells (Tregs). This strain-independent protection suggests that LGW modulates fundamental, early-stage immune signaling pathways within the liver. Conclusions: Our findings demonstrate that LGW exerts potent hepatoprotection by effectively reprogramming the hepatic immune microenvironment toward a tolerogenic state. These results position LGW as a promising, safe, and effective functional food candidate for the prevention and adjunct management of immune-mediated inflammatory liver diseases. Full article