Search Results (12,835)

Seed vigor is a key agronomic trait that integrates germination capacity and seedling establishment, critically influencing rice productivity. Inositol hexakisphosphate (IP₆) serves as a major phosphorus reservoir in seeds, yet its regulatory mechanism in seed vigor remains unclear. Here, we demonstrate that exogenous IP₆ application inhibited seed germination and seedling growth of japonica rice (Oryza sativa L. ssp. japonica cv. Zhonghua11) in a dose-dependent manner; 10 mM IP₆ reduced seed germination by 100%, while 100 μM IP₆ suppressed primary root length by 33.6% compared to the control. This inhibitory effect is likely mediated by antagonizing auxin signaling, as supported by suppressed DR5::GUS expression and altered transcription of auxin-responsive genes. OsIPK2, a key enzyme in IP₆ biosynthesis, showed high expression during early development in rice. RNA interference of OsIPK2 led to a 40.8–61.7% reduction in seed IP₆ content, 45.3–65% higher zinc (Zn) and iron (Fe) accumulation, and a 35.4–53.5% lower germination rate compared to wild-type (WT). Conversely, OsIPK2-RNAi seedlings exhibited enhanced growth and resistance to IP₆, which was associated with misregulation of auxin-responsive genes and a decrease in the repressive histone mark H3K27me3 at their loci. Furthermore, endogenous indole-3-acetic acid (IAA) levels significantly reduced in Ri-1 but unchanged in Ri-2, while abscisic acid (ABA) content and the IAA/ABA ratio remained unaltered compared to wild-type. Our findings reveal that OsIPK2 balances seed vigor and seedling development by modulating inositol phosphate metabolism, auxin responses, and epigenetic regulation, providing insights for improving seed quality in cereals. Whether the regulatory role of OsIPK2 in seed vigor is conserved across other rice subspecies requires further investigation. Full article

Breast cancer is a heterogeneous disease that exists in multiple subtypes, some of which still lack targeted and effective therapy. A major challenge is to unravel their underlying molecular mechanisms and bring to light novel therapeutic targets. In this study, we investigated the role of WNT-inducible signaling pathway protein 1 (WISP1) matricellular protein in the acquirement of an invasive phenotype by breast cancer cells. To this aim, we treated non-invasive MCF7 cells with WISP1 and assessed the expression levels of macrophage migration inhibitory factor (MIF) and its cellular receptor CD74. Next, we examined the expression of epithelial-to-mesenchymal transition (EMT) markers as well as molecular effectors of the tumor microenvironment, such as CD44, the main hyaluronan receptor that also acts as a co-receptor for MIF, the hyaluronan oncogenic network, and specific matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). The results showed that WISP1 potently induces the expression of MIF cytokine and affects the expression of specific extracellular matrix molecules with established roles in the promotion of malignant properties. Notably, Src kinases and MIF are critically involved in these processes. Collectively, the present study demonstrates for first time a WISP1/Src/MIF axis as well as its ability to induce an invasive phenotype in MCF7 cells and highlights novel cellular and molecular processes involved in the epithelial-to-mesenchymal transition and the development of invasive breast cancer. This suggests that specific cues from the tumor microenvironment can activate a migratory/invasive phenotype in a subpopulation of cells residing within the heterogeneous breast tumor. Full article

Declining Leydig cell steroidogenesis contributes to late-onset hypogonadism and to age-associated impairment of male reproductive health. Determinants of dysfunction extend beyond chronological aging. This review synthesizes recent experimental and translational evidence on cellular and molecular processes that compromise Leydig cell endocrine output and the interstitial niche that supports spermatogenesis. Evidence spanning environmental endocrine-disrupting chemicals (EDCs), obesity and metabolic dysfunction, and testicular aging is integrated with emphasis on oxidative stress, endoplasmic reticulum stress, mitochondrial dysregulation, apoptosis, disrupted autophagy and mitophagy, and senescence-associated remodeling. Across model systems, toxicant exposure and metabolic stress converge on impaired organelle quality control and altered redox signaling, with downstream loss of steroidogenic capacity and, in some settings, premature senescence within the Leydig compartment. Aging further reshapes the testicular microenvironment through inflammatory shifts and biomechanical remodeling and may erode stem and progenitor Leydig cell homeostasis, thereby constraining regenerative potential. Single-cell transcriptomic atlases advance the field by resolving Leydig cell heterogeneity, nominating subsets that appear more vulnerable to stress and aging, and mapping age-dependent rewiring of interstitial cell-to-cell communication with Sertoli cells, peritubular myoid cells, vascular cells, and immune cells. Many mechanistic insights derive from rodent in vivo studies and in vitro platforms that include immortalized Leydig cell lines, and validation in human tissue and human clinical cohorts remains uneven. Together, these findings frame mechanistically informed opportunities to preserve endogenous androgen production and fertility through exposure mitigation, metabolic optimization, fertility-preserving endocrine stimulation, and strategies that target inflammation, senescence, and regenerative capacity. Full article

Reactive oxygen species (ROS) are essential regulators of fertilization and early embryo development in mammals, including humans and various animal models, but they exert detrimental effects when produced in excess. In assisted reproductive technologies (ART), particularly in vitro fertilization (IVF), exposure to non-physiological conditions increases oxidative stress (OS), impairing gamete quality, embryo viability, and clinical outcomes. This review synthesizes experimental and clinical studies describing the endogenous and exogenous sources of ROS relevant to embryo development in IVF. Endogenous ROS arise from intrinsic metabolic pathways such as oxidative phosphorylation, NADPH oxidase, and xanthine oxidase. Exogenous sources include suboptimal laboratory conditions characterized by factors such as high oxygen tension, temperature shifts, pH instability, light exposure, media composition, osmolarity, and cryopreservation procedures. Elevated ROS disrupt oocyte fertilization, embryonic cleavage, compaction, blastocyst formation, and implantation by inducing DNA fragmentation, lipid peroxidation, mitochondrial dysfunction, and apoptosis. In addition, the review highlights how parental health factors establish the initial redox status of gametes, which influences subsequent embryo development in vitro. While antioxidant supplementation and optimized culture conditions can mitigate oxidative injury, the precise optimal redox environment remains a subject of ongoing research. This review emphasizes that future research should focus on defining specific redox thresholds and developing reliable, non-invasive indicators of embryo oxidative status to improve the success rates of ART. Full article

Malaria remains a major global health burden, and the emergence of resistance to blood stage antimalarials underscores the need for new interventions targeting earlier stages of the parasite’s life cycle. The pre-erythrocytic liver stage represents a critical bottleneck and an attractive target for chemotherapeutic and prophylactic interventions. In this study, we functionally characterized the putative E3 ubiquitin ligase Trophozoite Exported Protein 1 (TEX1; PBANKA_0102200) in Plasmodium berghei using gene knockout, tagging, and imaging approaches across the mosquito and liver stages. TEX1 knockout parasites (PbTEX1-KO) showed impaired development during mosquito-stage transitions, with significant reductions in ookinete formation, oocyst numbers, and sporozoites reaching the salivary glands. In hepatic stages, TEX1-KO parasites displayed reduced growth, abnormal nuclear division, and impaired liver stage maturation, ultimately leading to a dramatic decline in detached cell formation and blood stage infectivity. Endogenous C-terminal tagging of TEX1 with GFP and 3×HA revealed a discrete subnuclear localization pattern, indicating a critical role in DNA synthesis and/or mitotic regulation. Our findings reveal that TEX1 is required for nuclear replication and division and successful development in both the mosquito and liver stages of Plasmodium. Given its pivotal role and nuclear localization during hepatic schizogony, TEX1 represents a promising target for the development of liver stage antimalarial interventions. Full article

The emerging paradigm of “fusion of lifeforms” represents a transformative shift from conventional human–machine interfaces toward deeply integrated symbiotic systems, where biological and artificial components co-adapt structurally, energetically, informationally, and cognitively. This review systematically classifies multi-level perception systems within fusion of lifeforms into four functional categories: sensory and functional restoration, beyond-natural sensing, endogenous state sensing, and cognitive enhancement. We survey recent advances in neuroprosthetics, sensory augmentation, closed-loop physiological monitoring, and brain–computer interfaces, highlighting the transition from substitution to fusion. Despite significant progress, critical challenges remain, including multi-source heterogeneous integration, bandwidth and latency limitations, power and thermal constraints, biocompatibility, and system-level safety. We propose future directions such as layered in-body communication networks, sustainable energy strategies, advanced biointerfaces, and robust safety frameworks. Ethical considerations regarding self-identity, neural privacy, and legal responsibility are also discussed. This work aims to provide a comprehensive reference and roadmap for the development of next-generation fusion of lifeforms, ultimately steering human–machine integration from episodic functional repair toward sustained, multi-level symbiosis between biological and artificial systems. Full article

Aiming at the problems of tree vigor decline and unstable fruit quality caused by soil impoverishment and easy nutrient loss in the Ziziphus jujuba Mill. ‘Huizao’ (Huizao) producing areas of southern Xinjiang, the application effect of bag-controlled slow-release fertilizer (BCSRF) in this region remains unclear. In this study, a field experiment was conducted with four fertilization concentration gradients, including CK (0 kg/ha), T1 (22 kg/ha), T2 (44 kg/ha), and T3 (66 kg/ha), to investigate the effects of BCSRF on soil nutrient dynamics and plant growth, as well as the fruit yield and quality of Huizao. The results showed that BCSRF could effectively maintain the supply levels of soil alkali-hydrolysable nitrogen, available phosphorus, and available potassium during key growth periods, among which the T3 treatment exhibited the most significant effect. This treatment not only significantly increased the yield per plant of Huizao by 39.34% compared with the control, but also markedly enhanced the contents of the endogenous substance, including soluble sugar and cyclic adenosine monophosphate. This study confirms that under the condition of sandy loam soil in southern Xinjiang, a single basal application of an appropriate amount of BCSRF can achieve continuous nutrient supply, simultaneously improve soil fertility and fruit quality, providing a theoretical basis and technical guidance for simplified and efficient fertilization in local jujube orchards. Full article

In the context of the global pursuit of the ‘carbon neutrality’ objective, Chinese enterprises are proactively advancing green development and low-carbon transformation. Among these efforts, climate transition risks have emerged as a crucial factor affecting strategic enterprise decisions and long-term competitiveness. This study utilizes a sample comprising Chinese A-share listed enterprises over the period from 2012 to 2024 to construct an enterprise climate transition risk index using text analysis methods. It empirically investigates this index’s impact on enterprise green innovation by adopting panel data analysis method to construct a fixed effects model and further examines the moderating roles of institutional investors’ shareholding and enterprise environmental uncertainties in response to climate transition risks. The research findings indicate the following: First, climate transition risks significantly enhance enterprise green innovation. The validity of this conclusion persists following a series of robustness and endogeneity tests, including replacing the explained variable, lagging the explanatory variable, controlling for city-level fixed effects, and applying instrumental variable methods. Second, both institutional investors’ shareholding and enterprise environmental uncertainties exert a significant positive regulatory effect on the relationship between climate transition risk and green innovation, indicating that external monitoring and heightened risk perception jointly enhance enterprises’ responsiveness in driving green innovation. Thirdly, heterogeneity analysis indicates that the positive impact of climate transition risks on green innovation is notably amplified within non-state-owned enterprises and manufacturing enterprises. By examining the dual regulatory mechanisms of ‘external monitoring’ and ‘risk perception’, this study broadens the study framework on the relationship between climate risks and enterprise green innovation, offering new empirical evidence supporting the applicability of the ‘Porter Hypothesis’ within the context of climate-related challenges. Furthermore, it provides valuable implications for policymakers in refining climate information disclosure policies and assists enterprises in developing forward-looking green innovation strategies. Full article

Iodine deficiency remains a global public health concern. Preliminary studies confirmed that cauliflower can serve as a carrier for iodine salts. However, the influence of its endogenous goitrogenic compounds (phenolic compounds and glucosinolates) on iodine utilisation is not fully understood. This study aimed to assess the potential for enhancing cauliflower’s effectiveness as an iodine carrier through various thermal pre-treatment methods, and to examine how these methods, along with the plant’s endogenous goitrogens, affect iodine stability. Cauliflower was cooked by steaming or boiling (covered or uncovered) and fortified with KI or KIO₃. Iodine content, selected phenolic compounds (sinigrin, progoitrin, glucobrassicin, gluconapin, indole-3-carbinol) and antioxidant activity (ABTS^●+, DPPH^●) were analysed immediately after fortification and after 90 days of storage at 4, 21, or 40 °C under controlled humidity and darkness. The results showed that both the heat-treatment method and storage temperature significantly affected iodine retention and were associated with changes in goitrogenic compounds and antioxidant capacity. Cauliflower demonstrated favourable stability as a carrier of iodine, although phytochemical composition influenced fortification outcomes. These findings suggest that the initial heat treatment of cauliflower significantly affects its effectiveness as a matrix for iodine fortification, likely due to differences in the content of goitrogenic compounds. Full article

Background: Moderate physical activity (PA) exerts powerful systemic and neuroprotective effects, reducing chronic disease risk and enhancing cognitive and psychological well-being. PA promotes brain plasticity by upregulating neurotrophic factors and stimulating neurogenesis. Given the established role of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in neuronal survival, differentiation, and anti-apoptotic signaling, we aimed to investigate whether moderate PA modulates the endogenous expression of PACAP and its specific receptor PAC1R in the DG and cerebellar cortex. Methods: To this end, twenty-four rats were distributed into sedentary or exercise groups. Immunohistochemical and Western blot analyses were performed to assess PACAP and PAC1R expression. Co-expression with doublecortin (DCX), a marker of immature neurons, was evaluated to explore the direct relationship between PACAP signaling and neurogenesis. Results: Our results showed that moderate PA induced a significant up-regulation of PACAP and PAC1R in both the DG and cerebellar cortex compared to sedentary controls. Moreover, high co-expression of PACAP and DCX was detected in these regions, suggesting an involvement of PACAP in exercise-induced neurogenic processes. Conclusions: These findings demonstrate that moderate physical activity is associated with enhanced PACAP/PAC1R signaling and DCX expression in neurogenic regions, warranting further investigation into its specific contribution to exercise-induced brain plasticity. Full article

This study employs numerical simulations to analyse current densities in modelled human organs originating from extremely low frequency (ELF) electromagnetic fields emanating from a 110 kV single-circuit high-voltage transmission line. Exposure to these ELF fields gives rise to both conduction and displacement currents within the human body, potentially perturbing endogenous bioelectric currents and raising concerns of health risks. Using CST Studio Suite 2018 software, a three-dimensional multipart ellipsoidal anatomical model is developed to analyse these phenomena. Although displacement currents have lower magnitudes than conduction currents, they contribute significantly to the total current density and must therefore be included in rigorous safety assessments. Simulation results indicate that the current density values remain below the basic restrictions of the International Commission on Non-Ionizing Radiation Protection. Full article

This systematic review examines chronic kidney disease-associated pruritus (CKD-aP) as a complex clinical manifestation in patients undergoing hemodialysis. Traditionally considered a secondary symptom of end-stage renal disease, emerging evidence now positions CKD-aP as a multidimensional disorder with substantial pathogenic influence on patient outcomes. Using the PRISMA 2020 methodology, we critically evaluated 54 peer-reviewed studies published between 2020 and 2025. Our synthesis highlights a convergence of five mechanistic frameworks underpinning CKD-aP: elevated levels of uremic toxins originating from gut microbial dysbiosis, immune activation driven by IL-31 and other pro-inflammatory cytokines, heightened peripheral and central neural sensitization, dysregulation of endogenous opioid receptor pathways favoring μ-receptor activation, and xerosis-related epidermal barrier dysfunction. These mechanisms contribute to a systemic cycle of microinflammation, pruritogenic signaling, and neural hyperexcitability. We also identified and compared validated assessment tools—including the NRS, VAS, Skindex-10, and the UP-Dial scale—that facilitate standardized quantification of disease burden. While available treatments such as gabapentinoids and phototherapy offer partial relief, targeted therapies—including κ-opioid receptor agonists—represent a major advancement, although long-term effectiveness and accessibility remain under investigation. Growing scientific consensus establishes CKD-aP as a priority therapeutic target in hemodialysis care, underscoring the need for integrated, mechanism-based management strategies to improve quality of life and clinical outcomes. This work represents a narrative systematic review, integrating evidence from mechanistic, translational, and clinical studies to critically examine the biological pathways underlying CKD-associated pruritus. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are debilitating disorders with overlapping symptoms such as chronic pain and fatigue. Dysregulation of the endogenous opioid system, particularly µ-opioid receptor function, may contribute to their pathophysiology. This study examined whether epigenetic modifications, specifically µ-opioid receptor 1 gene (OPRM1) promoter methylation, play a role in this dysfunction. Using a repeated-measures design, 28 ME/CFS/FM patients and 26 matched healthy controls visited the hospital twice within four days. Assessments included blood sampling for epigenetic analysis, a clinical questionnaire battery, and quantitative sensory testing (QST). Global DNA (hydroxy)methylation was quantified via liquid chromatography–tandem mass spectrometry, and targeted pyrosequencing was performed on promoter regions of OPRM1, COMT, and BDNF. ME/CFS/FM patients reported significantly worse symptom outcomes. No differences in global (hydroxy)methylation were found. Patients showed significantly higher OPRM1 promoter methylation, which remained after adjusting for symptom severity and QST findings. Across timepoints, OPRM1 methylation consistently correlated with BDNF Promoter I and Exon III methylation. This is, to the best of our knowledge, the first study examining OPRM1 methylation in ME/CFS/FM. Increased OPRM1 methylation in patients, independent of symptoms or pain sensitivity measures, supports the hypothesis of dysregulated opioidergic signaling in these conditions. Full article

Nickel allergy remains the most prevalent cause of allergic contact dermatitis worldwide, imposing a substantial socio-epidemiological and economic burden. Beyond its classical cutaneous presentation, systemic nickel allergy syndrome highlights the systemic dimension of Nickel hypersensitivity, wherein dietary nickel intake may provoke both gastrointestinal and cutaneous symptoms through mechanisms involving gut barrier impairment and mucosal immune priming. Recent evidence highlights the contribution of angiogenesis and lymph-angiogenesis to Nickel-induced allergic contact dermatitis, through crosstalk among keratinocytes, mast cells, endothelial cells, and pro-angiogenic mediators such as vascular endothelial growth factor. Against this background, we propose to revisit palmitoylethanolamide, an endogenous ALIAmide with well-documented anti-inflammatory, anti-angiogenic, and anti-allergic properties. Already studied in pain and inflammatory disorders and employed in veterinary dermatology, palmitoylethanolamide down-modulates mast cell degranulation, suppresses VEGF expression via PPAR-α/Akt/mTOR signaling, and enhances intestinal barrier integrity, acting as a promising “gatekeeper” molecule that reduces gut hyperpermeability characterizing systemic nickel allergy as well as other gut disorders with systemic consequences. This paper is presented as a viewpoint intended to highlight the untapped therapeutic potential of palmitoylethanolamide, suitable for both oral and topical administration, as a candidate to address the multifactorial pathophysiology of Nickel allergic contact dermatitis and systemic nickel allergy. Our purpose is not to provide definitive answers, but to stimulate scientific debate on its rational use within emerging gut–skin therapeutic strategies. We thus encourage future experimental and clinical studies to explore its potential integration within emerging gut–skin therapeutic paradigms. Full article

(1) Background: The naked mole-rat (Heterocephalus glaber) survives hypoxia–reoxygenation stresses by utilizing metabolic rate depression, achieved in part by downregulating nonessential genes and processes to conserve endogenous cellular resources and prevent buildup of toxic waste byproducts. Tight molecular control of protein degradation (specifically the ubiquitin–proteasome system) is a potent regulatory tool for maintaining muscle integrity during hypoxia, but how this system is regulated in the heart of hypoxia-tolerant species is poorly understood. (2) Methods: The protein expression levels of cullin-RING E3 ligases (specifically CRL4 architecture), deubiquitinating enzymes, and proteasomal activity were assayed in cardiac tissues from H. glaber exposed to 24 h of normoxia or hypoxia in vivo. (3) Results: Overall, the protein expression of E3 ligases decreased, whereas expression of deubiquitinating enzymes increased during hypoxia, all of which play roles in themes of oxidative stress, heightened DNA damage repair, and the HIF-1-VHL-NFκB axis. Proteasomal activity was elevated during hypoxia, which conceivably links to the oxidative stress theory of aging and longevity of H. glaber. (4) Conclusions: Taken together, our results expand current research into protein degradation and extreme environmental stress responses, with a specific focus on cardiac mechanisms related to oxidative stress resistance along the hypoxia-longevity axis. Full article