Search Results (2,226)

To elucidate the comprehensive mechanism by which nitric oxide (NO) enhances low-temperature tolerance in cucumber, we utilized two cucumber cultivars (Jinyan No. 4 and Jinyou No. 1) as experimental materials. By integrating transcriptomic analysis with physiological indicators, we investigated the physiological and molecular mechanisms underlying the NO-mediated improvement of cold tolerance. Both molecular and physiological data revealed that phytohormone signal transduction and alpha-linolenic acid metabolism were significantly affected by low-temperature stress alone and in combination with exogenous SNP treatment in both cultivars. Under low-temperature stress, most transcripts associated with abscisic acid (ABA) biosynthesis, ABA signal transduction, and flavonoid biosynthesis were coordinately downregulated in cucumber. In contrast, transcripts related to secondary metabolism, lipid metabolism, glutathione biosynthesis, and hormone signal transduction—including salicylic acid (SA), ethylene (ETH), gibberellin (GA), and jasmonic acid (JA) pathways—were coordinately upregulated. Additionally, exogenous SNP was found to regulate both phytohormone signal transduction and endogenous hormone levels. These results suggest that exogenous NO improves low-temperature tolerance in cucumber seedlings primarily by modulating phytohormone signaling and secondary metabolism. Full article

The ongoing challenge of doping in sports has triggered the adoption of advanced scientific strategies for the detection and prevention of doping abuse. This review examines the potential of integrating metabolomics aided by artificial intelligence (AI) and machine learning (ML) for profiling small-molecule metabolites across biological systems to advance anti-doping efforts. While traditional targeted detection methods serve a primarily forensic role—providing legally defensible evidence by directly identifying prohibited substances—metabolomics offers complementary insights by revealing both exogenous compounds and endogenous physiological alterations that may persist beyond direct drug detection windows, rather than serving as an alternative to routine forensic testing. High-throughput platforms such as UHPLC-HRMS and NMR, coupled with targeted and untargeted metabolomic workflows, can provide comprehensive datasets that help discriminate between doped and clean athlete profiles. However, the complexity and dimensionality of these datasets necessitate sophisticated computational tools. ML algorithms, including supervised models like XGBoost and multi-layer perceptrons, and unsupervised methods such as clustering and dimensionality reduction, enable robust pattern recognition, classification, and anomaly detection. These approaches enhance both the sensitivity and specificity of diagnostic screening and optimize resource allocation. Case studies illustrate the value of integrating metabolomics and ML—for example, detecting recombinant human erythropoietin (r-HuEPO) use via indirect blood markers and uncovering testosterone and corticosteroid abuse with extended detection windows. Future progress will rely on interdisciplinary collaboration, open-access data infrastructure, and continuous methodological innovation to fully realize the complementary role of these technologies in supporting fair play and athlete well-being. Full article

Background: Several studies suggest that exogenous oxytocin nasal spray may enhance placebo analgesia in healthy volunteers and experimental pain models, although the findings remain mixed. The oxytocin placebo hypothesis suggests that increased oxytocin levels trigger a cascade of brain processes that boost positive expectations and augment the placebo response. Since endogenous oxytocin secretion has been found to increase during positive interactions, we hypothesized that changes in endogenous oxytocin levels will affect placebo analgesia in chronic-back-pain patients. Given the role sex has in both placebo analgesia and oxytocin secretion, we hypothesized that the response magnitude will differ by sex. Methods: Chronic-back-pain patients (n = 112) were prospectively recruited and received placebo injections. The placebo response was calculated as the change in the back-pain Visual Analog Score (VAS), and changes between pre- and post-injection salivary oxytocin levels were measured. The effect of sex and changes in oxytocin levels on pain reduction was calculated using two-way analysis of variance (ANCOVA). Results: Oxytocin levels decreased in 62.5% of participants and increased in 37.5%. Increased oxytocin levels were associated with greater pain reduction than decreased oxytocin levels (p = 0.024). Females exhibited greater pain reduction than males (p = 0.034). No interaction between the oxytocin change pattern and sex was observed. Conclusions: This study demonstrates that following a placebo injection, patients suffering from chronic back pain, who exhibited an increase in endogenous oxytocin levels, showed a higher placebo response. Females had a greater placebo response, but this was not associated with an endogenous oxytocin change. These results provide initial support for the oxytocin placebo hypothesis. Full article

C-type natriuretic peptide (CNP), encoded by the NPPC (Natriuretic Peptide Precursor C), has been recognized as the principal endogenous factor sustaining oocyte meiotic arrest in mammalian follicles. Yet its influence on porcine ovarian granulosa cell fate and the regulatory mechanism of NPPC expression within these cells remain poorly understood. Here, utilizing an in vitro culture model of primary porcine ovarian granulosa cells and immature oocytes, we examined the impact of CNP on granulosa cell apoptosis and oocyte meiotic resumption, and elucidated the molecular circuitry governing NPPC expression. We found that follicular atresia in pigs was accompanied by a marked decline in the CNP receptor NPR2 (natriuretic peptide receptor 2). Correspondingly, exogenous CNP suppressed apoptosis in cultured porcine granulosa cells. Estradiol can significantly promote the expression level of NPPC in porcine ovarian granulosa cells and, by enhancing NPR2 levels, it can synergize with CNP to inhibit oocyte meiotic resumption in vitro. Conversely, EGF signaling can significantly downregulate NPPC mRNA expression in porcine granulosa cells, an effect likely mediated by ERK-activated tristetraprolin (TTP). Collectively, these findings broaden our understanding of CNP in follicular development and delineate the endocrine network that controls NPPC transcription in the porcine ovary. Full article

Exosomes, naturally derived extracellular vesicles, have emerged as powerful bio-nanocarriers in precision medicine. Their endogenous origin, biocompatibility, and ability to encapsulate and deliver diverse therapeutic payloads position them as transformative tools in drug delivery, gene therapy, and regenerative medicine. This review presents a comprehensive analysis of exosome-based therapeutics across multiple biomedical domains, including cancer, neurological and infectious diseases, immune modulation, and tissue repair. Exosomes derived from stem cells, immune cells, or engineered lines can be loaded with small molecules, RNA, or CRISPR-Cas systems, offering highly specific and low-immunogenic alternatives to viral vectors or synthetic nanoparticles. We explore endogenous and exogenous loading strategies, surface functionalization techniques for targeted delivery, and innovations that allow exosomes to traverse physiological barriers such as the blood–brain barrier. Furthermore, exosomes demonstrate immunomodulatory and regenerative properties in autoimmune and degenerative conditions, with promising roles in skin rejuvenation and cosmeceuticals. Despite their potential, challenges remain in large-scale production, cargo loading efficiency, and regulatory translation. Recent clinical trials and industry efforts underscore the accelerating momentum in this field. Exosomes represent a promising platform in precision medicine, though further standardization and validation are required before widespread clinical use. This review offers critical insights into current technologies, therapeutic mechanisms, and future directions to unlock the full translational potential of exosomes in clinical practice. Full article

The human microbiome is a critical factor in health and disease. While its association with breast cancer (BC) has been increasingly studied, this review provides a dedicated synthesis of the microbiota’s role in benign breast diseases (BBDs)—a common yet microbiologically overlooked spectrum of conditions. The primary aim of this work is to consolidate the current understanding of the composition, origins, and functional mechanisms of the mammary gland (MG) microbiota specifically in the context of BBD and to evaluate its potential for novel diagnostic and therapeutic targets. We detail the distinct MG microbiota, formed via exogenous (e.g., cutaneous, translocation) and endogenous (e.g., enteromammary, lymphohematogenous) pathways, and its interaction with the host through estrogen metabolism, immunomodulation, and epigenetic modifications. This narrative review reveals unique dysbiotic patterns in BBD, characterized by distinct microbial signatures, such as the enrichment of Corynebacterium kroppenstedtii in granulomatous mastitis and the presence of Staphylococcus aureus in fibroadenomas and lactational mastitis. Furthermore, specific gut microbial profiles are identified in BBD patients, including an increased abundance of genera such as Clostridium and Faecalibacterium, alongside a decrease in Collinsella and Alistipes compared to healthy controls. These specific taxa represent compelling candidates for diagnostic biomarkers. We conclude that microbial dysbiosis is a significant component of BBD pathogenesis. A paradigm shift toward multi-omics approaches and mechanistic studies is now essential to translate these associations into clinical applications. Understanding the BBD-specific microbiome holds the promise of revolutionizing patient care through microbiota-based diagnostics for differentiating benign subtypes and novel, personalized therapeutic strategies aimed at restoring microbial homeostasis. Full article

Human DNA is continuously exposed to endogenous and exogenous agents that generate over 100,000 lesions per cell each day. In addition to damage to nucleobases, deoxyribose, and phosphate groups, a particularly harmful class of lesions involves non-canonical DNA termini—structures deviating from the canonical 3′-hydroxyl and 5′-phosphate ends. These aberrant DNA ends can obstruct essential DNA transactions and, if left unrepaired, contribute to cytotoxicity and mutagenesis. Their biological significance is further highlighted by the severe pathologies linked to deficiencies in DNA end-processing enzymes, including inflammation, cancer predisposition syndromes, neurodegeneration, and aging. This review highlights recent advances in our understanding of the formation, prevalence, and repair mechanisms of several key non-canonical DNA end structures, including 3′-phosphate, 3′-phosphoglycolate, 3′-α,β-unsaturated aldehyde and its glutathione derivative, 5′-deoxyribose-5-phosphate, 2′-deoxyribonucleoside-5′-aldehyde, and 5′-adenosine monophosphate. These non-canonical DNA terminal structures arise from various sources, such as radical-induced oxidation of the 2-deoxyribose moiety and DNA repair pathways. While this review does not cover the full spectrum of non-canonical termini, the selected structures are emphasized based on quantitative data supporting their biological relevance. The review also discusses their broader implications in mitochondrial DNA maintenance and inflammatory signaling and highlights key knowledge gaps that warrant further investigation. Full article

To understand the changes in gonadal sex differentiation, digestive enzyme activity, and growth-related hormone levels in the larval and juvenile black scraper, Thamnaconus modestus, continuous sampling was conducted from 0 to 91 days post-hatching (dph). 17β-estradiol (E2) and testosterone (T) levels, six digestive enzymes, as well as T3, T4, GH, and IGF-I were detected. The results showed that oogonia or spermatogonia was observed at 60 dph. During the sex differentiation to female or male, both E2 and T levels significantly increased (p < 0.05), suggesting that E2 and T may induce the sex differentiation to female or male in T. modestus, respectively. The amylase activity from 0 to 35 dph showed a slow upward trend, which may be due to the transition from endogenous to exogenous nutrition at this time. From 12 to 25 dph, alkaline protease activity significantly decreased (p < 0.05), while acid protease levels significantly increased (p < 0.05), suggesting that as organs in the digestive system continue to develop, acid protease plays an important role. T3 and T4 could already be detected at 0 dph, and the T4 content was always much higher than T3 throughout the stages, indicating that T4 may play more important roles than T3. Additionally, the changes in IGF-I and GH content followed a trend of an initial increase, a subsequent decrease, and then an increase, ultimately showing an overall upward trend. These results indicate that T4, IGF-I, and GH play crucial roles in growth and development in the juvenile fish. In conclusion, the results of this study provide useful information for growth, artificial reproduction, and sex regulation in T. modestus. Full article

Nutritional factors play a crucial role in many gynecological disorders, particularly those influenced by estrogen. Uterine fibroids are benign tumors that affect a large proportion of women of reproductive age, especially between 30 and 40 years. These lesions may cause significant symptoms, including pelvic pain, heavy menstrual bleeding, and infertility. In younger women, the onset of fibroids is often associated with familial and genetic predisposition, whereas in adulthood, hormonal influences linked to environmental factors and states of exogenous or endogenous hyperestrogenism are more frequently observed. In both contexts, supportive management through an appropriate diet may provide clinical benefit. Although the precise pathogenesis remains incompletely understood, hormonal, genetic, and environmental components—particularly hyperestrogenism—are considered key contributors to fibroid development. Current evidence suggests that consumption of saturated fats, particularly from red meat and full-fat dairy, may raise circulating estrogen concentrations and contribute to the development of fibroids. In contrast, diets abundant in fiber, fruits, and vegetables appear to exert a protective effect, potentially lowering fibroid risk. Obesity, through increased aromatization and consequent estrogen production, also represents an established risk factor. This narrative review aims to explore the role of nutritional determinants in the onset and progression of uterine fibroids, with a specific focus on the impact of individual nutrients, foods, and dietary patterns on clinical outcomes. Particular emphasis is placed on obesity and macronutrient composition (e.g., high-fat versus high-fiber dietary regimens) as potential modulators of circulating estrogen levels and, consequently, fibroid growth dynamics. Furthermore, the potential of nutritional strategies as complementary therapeutic approaches, capable of integrating established clinical practices, is examined. Full article

Against the backdrop of global agricultural transformation, rural China faces the critical challenge of reconciling economic development with environmental conservation and social well-being. This study, grounded in the rural revitalization strategy, investigates the internal mechanisms, level measurement, and sustainable development paths of rural industrial integration based on the “Triple Integration of Production, Livelihood and Ecology” (PLE) philosophy. Firstly, we discussed the suitability and the mechanisms of this philosophy on China’s rural industrial integration. Secondly, based on a textual corpus extracted from academic journals and policy documents, we employed an LDA topic model to cluster the themes and construct an evaluation indicator system comprising 29 indicators. Then, utilizing data from the China Statistical Yearbook and the China Rural Statistical Yearbook (2013–2022), we measured the level of China’s rural industrial integration using the entropy method. The composite integration index displays a continuous upward trend over 2013–2022, accelerating markedly after the 2015 stimulus policy, yet a temporary erosion of “production–livelihood–ecology” synergy occurred in 2020 owing to an exogenous shock. Lastly, combining the system dynamics model, we simulated over the period 2023–2030 the three sustainable development scenarios: green ecological development priority, livelihood standard development priority and production level development priority. Research has shown that (1) the “Triple Synergy of Production, Livelihood and Ecology” philosophy and China’s rural industrial integration are endogenously unified, and they form a two-way mutual mechanism with the common goal of sustainable development. (2) China’s rural industrial integration under this philosophy is characterized by production-dominated development and driven mainly by processing innovation and service investment, but can be constrained by ecological fragility and external shocks. (3) System dynamics simulations reveal that the production-development priority scenario (Scenario 3) is the most effective pathway, suggesting that the production system is a vital engine driving the sustainable development of China’s rural industrial integration, with digitalization and technological innovation significantly improving integration efficiency. In the future, efforts should focus on transitioning towards a people-centered model by restructuring cooperative equity for farmer ownership, building community-based digital commons to bridge capability gaps, and creating market mechanisms to monetize and reward conservation practices. Full article

Background/Objectives: The prebiotic effect of resistant potato starch (RPS) has been demonstrated, but the antioxidant properties associated with this ingredient have not been explored. Methods: We performed post hoc analysis of serum metabolomic data from a clinical trial evaluating 3.5 g RPS per day consumption (n = 24) versus a placebo (n = 24) for 4 weeks in a randomized clinical trial (NCT05242913). Results: Levels of the exogenous antioxidants all-trans retinol and α-tocopherol increased in the RPS-consuming group. Among endogenous antioxidants, the concentration of coenzyme Q10 (CoQ10) increased in both treatment groups, while uric acid was unaffected. Hippuric acid, a marker of polyphenol metabolism, was unaffected by treatment, as was the abundance of the tryptophan metabolites kynurenine and 3-hydroxyanthranillic acid. However, levels of 3-hydroxykynurenine were decreased in both treatment groups. Levels of the advanced glycation end products NƐ-(1-carboxymethyl)-L-lysine and NƐ-(1-carboxyethyl)-L-lysine, markers of chronically elevated oxidative stress, were unaffected by treatment. Notably, increases in serum all-trans retinol were correlated with increases in Akkermansia. Conclusions: RPS enhances the absorption of antioxidants all-trans retinol and α-tocopherol from the diet and also influences CoQ10 levels and tryptophan metabolism. Future studies assessing the physiological consequences of enhanced antioxidant absorption in people consuming RPS over a longer duration are warranted. Full article

Cytokinins (CKs) are central regulators of leaf senescence, yet their cultivar-specific functions in cereals remain insufficiently understood. Here, we examined dark-induced senescence (DIS) in three barley (Hordeum vulgare L.) cultivars: Carina, Lomerit, and Bursztyn, focusing on responses to exogenous benzyladenine (BA) and inhibition of endogenous CK biosynthesis via the mevalonate (MVA) pathway using lovastatin (LOV). Bursztyn, a winter cultivar, displayed a previously uncharacterized stay-green phenotype, characterized by delayed chlorophyll and protein degradation and reduced sensitivity to BA with respect to chlorophyll retention. In contrast, Carina (spring) senesced rapidly but exhibited strong responsiveness to BA. Lomerit (winter) showed an intermediate phenotype, combining moderate natural resistance to senescence with clear responsiveness to BA. CK application suppressed SAG12 cysteine protease accumulation in all cultivars, serving as a marker of senescence and N remobilization, stabilized photosystem II efficiency, preserved photosynthetic proteins, and alleviated oxidative stress without promoting excessive energy dissipation. Although BA only partially mitigated the decline in net CO₂ assimilation, it sustained ribulose-1,5-bisphosphate regeneration, supported electron transport, and stabilized Rubisco and Rubisco activase. Moreover, LOV-based inhibition of the MVA pathway of CK biosynthesis revealed that endogenous CK contributions to senescence delay were most pronounced in Lomerit, moderate in Bursztyn, and negligible in Carina, indicating genotype-specific reliance on MVA-versus methylerythritol phosphate (MEP) pathway-derived CK pools. Collectively, these findings identify Bursztyn as a novel genetic resource for stay-green traits and demonstrate that BA delays DIS primarily by maintaining photosynthetic integrity and redox balance. The results highlight distinct regulatory networks shaping CK-mediated senescence responses in cereals, with implications for improving stress resilience and yield stability. Full article

Fusarium wilt, caused by Fusarium oxysporum f. sp. phaseoli (Fop), is a major constraint to global common bean (Phaseolus vulgaris L.) production. Thiamine (vitamin B1), an essential coenzyme in plant metabolism, has recently emerged as a potential regulatory factor in plant defense. Here, we performed a comprehensive genome-wide analysis of thiamine biosynthesis-related genes in common bean and elucidated their roles in resistance to Fusarium wilt. Five key thiamine biosynthetic genes were identified and characterized, showing conserved functional domains and evolutionary conservation across species. Expression profiling revealed tissue-specific patterns, with PvTHI1-1 and PvTHIC being highly expressed in reproductive and photosynthetic organs, with their relative expression levels 0.28–0.57 higher than other members in the same tissue, while PvTPK maintained a basal expression level in the roots. Upon Fop infection, resistant genotypes exhibited significantly higher expression of thiamine biosynthetic genes and greater accumulation of endogenous thiamine and its derivatives than susceptible ones. Functional analysis using Agrobacterium rhizogenes-mediated transformation demonstrated that overexpression of PvTPK enhanced thiamine metabolism and conferred resistance in susceptible genotypes. Similarly, exogenous application of thiamine upregulated biosynthetic genes and improved disease resistance. Together, these results reveal that thiamine biosynthesis is intricately linked to Fusarium wilt resistance and that both genetic and biochemical manipulation of thiamine pathways can enhance disease tolerance. This study provides new insights into thiamine-mediated plant immunity and establishes a foundation for its application in the control of Fusarium wilt in common bean. Full article

Background: Parkinson’s disease (PD) is a neurodegenerative disorder affecting men more frequently than women, a difference that might be due to many factors, including sexual hormones. Estrogens seem to confer a protective effect on the nigrostriatal pathway in experimental studies but their effects on cognition in patients with PD are unknown. Aim: To investigate the impact of the exogenous and endogenous estrogens on cognitive impairment in women with PD. Methods and materials: We recruited and consecutively interviewed outpatient women affected by PD. Each patient underwent a cognitive assessment via the Montreal Cognitive Assessment scale (MoCA), an anamnestic collection of the reproductive lifespan variables and clinical features. We investigated if some of the reproductive lifespan variables investigated could predict cognition outcomes in post-menopausal women with PD. Results: A total of 90 women with PD were recruited. Women with MoCA ≥ 26 (n = 27) had a lower median age at menarche (11 [11,12] vs. 13 [12–14], p < 0.0001), lower disease duration in years (8.3 [6.1–12.7] vs. 9.4 [6–12.7], p = 0.6), and less advanced disease (1 [1,2] vs. 2 [1–3], p = 0.02). Among all the reproductive life-span variables, only earlier age at menarche significantly predicted higher scores on MoCA (aOR = 0.5 [0.3–0.8], p = 0.005). No other clinical and reproductive factors have been shown to have an influence on cognitive scores. Conclusions: Age at menarche correlated with cognitive outcomes. Our study suggests that earlier exposure to endogenous estrogens during a phase of development and plasticity of the brain might preserve women with PD from cognitive decline. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with poor clinical outcomes. microRNA-7-5p (miR-7-5p) has been described as both a tumour suppressor and an oncomiR depending on the tissue context, but its role in HNSCC remains unclear. This study aimed to clarify the clinical significance and biological function of miR-7-5p in HNSCC by integrating data from multiple sources. Methods: A systematic review of the literature was conducted to identify studies analysing miRNA expression in human head and neck tissues. A meta-analysis of individual patient data from Gene Expression Omnibus (GEO), ArrayExpress, and The Cancer Genome Atlas (TCGA) was performed to assess miR-7-5p expression in tumours and normal tissues, and its associations with clinical parameters and prognostic outcomes. Bioinformatics analyses were used to predict miR-7-5p target genes, classify hub genes, and perform gene ontology enrichment analysis. MicroRNA in situ hybridisation (miRNA ISH) and real-time quantitative PCR (RT-qPCR) were conducted on tissue samples, HNSCC cell lines, and an in vitro model of oral oncogenesis to validate miR-7-5p expression patterns. Results: miR-7-5p was significantly upregulated in tumours compared to normal tissues and associated with larger tumour size, HPV-negative status, poor disease-specific survival, and shorter progression-free intervals. Bioinformatics analysis highlighted miR-7-5p target genes enriched in pathways related to cell growth, survival, and tumourigenesis. Despite evidence supporting the anti-cancer role of exogenous miR-7-5p in preclinical models, the observed endogenous upregulation in tumours suggests that miR-7-5p expression may represent a compensatory or stress-responsive mechanism during tumourigenesis, rather than acting as a primary oncogenic driver. Conclusions: This study provides new insights into the complex role of miR-7-5p in HNSCC, supporting its potential as both a biomarker and a therapeutic target. Understanding the context-specific functions of miR-7-5p is essential for its development as an RNA-based therapeutic in HNSCC. Full article