Search Results (36,187)

The use of hydrogel and biostimulants holds great potential for plants’ adaptation to stressful urban conditions, increasing their tolerance to drought stress. In this study, we investigated the plant performance and anatomical response of Petunia × hybrida hort. ex E. Wilm., cultivated under different substrate volumes and compositions, hydrogel amendments, and biostimulant treatments, as well as their interactions under drought stress. Namely, the plants were planted in pots with a substrate depth of 7 cm and 10 cm and cultivated under different combinations of organic (peat) and inorganic (perlite) substrates. Moreover, half of the plants were subjected to hydrogel and biostimulant treatments. Different watering intervals (24–96 h) were applied in combination with exposing the plants to direct sunlight for 8–10 h. The results showed that a larger substrate depth, along with hydrogel and biostimulant amendments in a mixture of perlite and peat, helps plants adapt to dry conditions when grown in shallow substrates, providing optimal water availability and thus contributing to the physiological adaptation of plants to water deficit. The study clearly demonstrates that substrate selection and irrigation frequency must be jointly optimized to ensure resilient urban greening. Hydrogels stand out as essential amendments, enabling significant water savings by extending irrigation intervals without compromising vascular growth or drought resilience. These water-efficient substrate strategies are vital for sustainable urban vegetation management, especially as cities face increasing environmental pressures and the imperative of climate adaptation, thereby supporting multiple Sustainable Development Goals. Full article

Apelin-13, a neuropeptide, has been recognized for its neuroprotective properties. Our previous study found apelin-13 improves cognitive function in Alzheimer’s disease (AD) rats by inhibiting neuroinflammation through upregulation of BDNF/TrkB signaling pathway. However, the precise mechanism by which apelin-13 modulates BDNF remains unclear. Thus, this study aimed to unravel the specific regulatory mechanism by which apelin-13 regulates BDNF. Bilaterally intracerebroventricular injection with Aβ25–35 was used to establish an in vivo model of AD. For the generation of METTL3 KO rats, the Crispr/Cas9 method was applied. PC12 cells were treated with Aβ25–35 to establish an in vitro model of AD. The cognitive function of the rats was evaluated with the Morris water maze and the novel object recognition test. Hippocampal damage and neuron loss were detected through H&E and immunofluorescent staining. METTL3, BDNF, TrkB, and p-TrkB were examined by Western blotting. Inflammation-related cytokines, IBA1, GFAP, IL-1β, and TNF-α were detected by Western blotting, immunofluorescent staining, ELISA, and qRT-PCR. m6A modification level was evaluated through MeRIP. A flow cytometer was applied to evaluate cell apoptosis. Cell proliferation was examined using MTT. m6A methylation inhibitor DAA reverses the improvement effect of apelin-13 on cognitive function, hippocampal nerve damage, neuron loss, and neuroinflammation in Aβ25–35-treated rats. Further results showed that apelin-13 upregulated METTL3, BDNF-AS m6A methylation, inhibited BDNF-AS expression, and subsequently upregulated BDNF/TrkB signaling pathway and reduced neuroinflammation in in vivo and in vitro AD models in a dose-dependent manner. Knockdown of METTL3 abolished apelin-13’s improvement effect in AD rats. Apelin-13-mediated upregulation of METTL3 enhances neuroinflammation inhibition and BDNF/TrkB signaling pathway via m6A-dependent downregulation of lncRNA BDNF-AS, thus ameliorating AD. Our study offers novel insights into the pathogenesis of AD and identifies potential drug targets for its treatment. Full article

Background: Epigenetic mechanisms and RNA signalling profoundly impact body growth during the early stages of embryonic development. RNA molecules, like microRNAs, play a vital role in early embryonic development, laying the groundwork for future growth and function. miR-124-3p microinjected into mouse fertilised eggs (miR-124-3p*) exhibited a significantly overgrowth phenotype. Behavioural test results showed that miR-124-3p mice were more physically active, as indicated by total distance and movement velocity. However, the molecular mechanism leading to these phenotypic changes mediated by miR-124-3p remains a mystery. This study aimed to investigate the role of epidermal growth factor (EGF) in developing an overgrowth phenotype in miR-124-3p* mice. Results: In this research, we preferred to work with neurospheres (NSs) due to the challenges of handling a single embryo, as NSs exhibit similar features, especially regarding cell growth, differentiation, and capacity for self-renewal. We examined the mRNA expression levels of Sox8, Sox9, Sox10, Doublecortin (Dcx), and Neurod1 genes, which are linked to a tiny phenotype in knockout mice, in total embryos at E7.5 and hippocampal cells isolated from E19.5-day fetus and neurospheres aged 12 and 21 days, which were derived from these hippocampal cells through primary cell culture. These genes are significantly overexpressed in miR-124-3p* NSs, but not in the E7.5 total embryos or the hippocampus of the E19.5 fetus. Conclusions: These findings suggest a possible link between miR-124-3p microinjection and EGF activation, which may be associated with early neurogenesis and neuronal differentiation in embryos. This molecular shift might contribute to the development of mice exhibiting increased physical activity and enlarged body size, although these observations remain correlative and require further validation. Full article

Ovarian aging is characterized by a gradual decline in both reproductive and endocrine functions, ultimately culminating in the cessation of ovarian activity around the age of 50, when most women experience natural menopause. The decline begins early, as follicular attrition is initiated in utero and continues throughout childhood and reproductive life. Most follicles undergo atresia without progressing through substantial stages of growth. With increasing age, a pronounced reduction occurs in the population of resting follicles within the ovarian reserve, accompanied by a decline in the size of growing follicular cohorts. Around the age of 38, the rate of follicular depletion accelerates, sometimes resulting in diminished ovarian reserve (DOR). The subsequent menopausal transition involves complex, irregular hormonal dynamics, manifesting as increasingly erratic menstrual patterns, primarily driven by fluctuations in circulating estrogens and a rising incidence of anovulatory cycles. In parallel with the progressive depletion of the follicular pool, the serum concentrations of anti-Müllerian hormone (AMH) decline gradually, while reductions in inhibin B levels become more apparent during the late reproductive years. The concomitant decline in both inhibin B and estrogen levels leads to a compensatory rise in circulating follicle-stimulating hormone (FSH) concentrations. Together, these endocrine changes, alongside the eventual exhaustion of the follicular reserve, converge in the onset of menopause, which is defined by the absence of menstruation for twelve consecutive months. The mechanisms contributing to ovarian aging are complex and multifactorial, involving both the oocyte and the somatic cells within the follicular microenvironment. Oxidative stress is thought to play a central role in the age-related decline in oocyte quality, primarily through its harmful effects on mitochondrial DNA integrity and broader aspects of cellular function. Although granulosa cells appear to be relatively more resilient, they are not exempt from age-associated damage, which may impair their hormonal activity and, given their close functional relationship with the oocyte, negatively influence oocyte competence. In addition, histological changes in the ovarian stroma, such as fibrosis and heightened inflammatory responses, are believed to further contribute to the progressive deterioration of ovarian function. A deeper understanding of the biological processes driving ovarian aging has facilitated the development of experimental interventions aimed at extending ovarian functionality. Among these are the autologous transfer of mitochondria and stem cell-based therapies, including the use of exosome-producing cells. Additional approaches involve targeting longevity pathways, such as those modulated by caloric restriction, or employing pharmacological agents with geroprotective properties. While these strategies are supported by compelling experimental data, robust clinical evidence in humans remains limited. Full article

Aging, a state of progressive decline in physiological function, is an important risk factor for chronic diseases, ranging from cancer and musculoskeletal frailty to cardiovascular and neurodegenerative diseases. Understanding its cellular basis is critical for developing interventions to extend human health span. This review highlights the crucial role of in vitro models, discussing foundational discoveries like the Hayflick limit and the senescence-associated secretory phenotype (SASP), the utility of immortalized cell lines, and transformative human induced pluripotent stem cells (iPSCs) for aging and disease modeling and rejuvenation studies. We also examine methods to induce senescence and discuss the distinction between chronological time and biological clock, with examples of applying cells from progeroid syndromes and mitochondrial diseases to recapitulate some signaling mechanisms in aging. Although no in vitro model can perfectly recapitulate organismal aging, well-chosen models are invaluable for addressing specific mechanistic questions. We focus on experimental strategies to manipulate cellular aging: from “steering” cells toward resilience to “reversing” age-related phenotypes via senolytics, partial epigenetic reprogramming, and targeted modulation of proteostasis and mitochondrial health. This review ultimately underscores the value of in vitro systems for discovery and therapeutic testing while acknowledging the challenge of translating insights from cell studies into effective, organism-wide strategies to promote healthy aging. Full article

Background: This study aimed to evaluate the cytotoxicity of bulk-fill composite materials compared to conventional compomers on stem cells from human exfoliated deciduous teeth. Methods: 90 standardized resin composite discs (4 mm thick, 4 mm diameter) were fabricated using a 3D-printed plate, comprising four bulk-fill composites (SDR, Tetric EvoCeram Bulk-Fill, VisCalor Bulk, Cention-N) and one compomer (Dyract XP). Samples were polymerized per the manufacturer’s instructions and sterilized. Stem cells were isolated from the pulp of exfoliated primary teeth. Cells were cultured and exposed to extracts of the composite materials soaked in culture medium for 24 h. Cytotoxicity was assessed using the MTT colorimetric assay, measuring cell viability via mitochondrial activity, and the Annexin V assay, quantifying apoptosis and necrosis via flow cytometry. Statistical analysis was performed using ANOVA and Tukey post hoc tests. Results: All materials significantly reduced cell viability compared to the control (p < 0.05), with optical density values indicating high cytotoxicity. Tetric EvoCeram exhibited the lowest necrosis and apoptosis levels, while Dyract XP showed the highest necrosis. Statistical analysis revealed no significant cytotoxicity differences among most bulk-fill composites (p < 0.05). Conclusion: Bulk-fill composites and conventional compomer tested exhibit comparable and significant cytotoxic effects on stem cells from human exfoliated primary teeth pulp. While these materials offer clinical advantages in pediatric dentistry due to ease and speed of application, their use underscores the dilemma of balancing operative efficiency with biological safety, and their cytotoxic profiles should be taken into consideration prior to application. Full article

Emerging evidence suggests that vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors exert synergistic immunomodulatory, anti-inflammatory and antioxidant actions. Moreover, intervention studies showed that combination therapy based on the concomitant use of vitamin D and DPP-4 inhibitors (VIDPP-4i) may preserve beta-cell function in patients with type 1 diabetes mellitus (T1D) and latent autoimmune diabetes in adults (LADA). These effects are particularly relevant in the context of beta-cell replacement strategies, whose long-term efficacy can be hampered by various factors, such as immune-mediated graft rejection, inadequate vascularization, hypoxia, trauma-induced cell apoptosis, fibrosis, host immune response, and recurrence of autoimmunity. Based on preclinical and clinical studies conducted in the fields of autoimmune diabetes and solid organ/cell transplantation, the present narrative review aims to describe the rationale behind the investigation of VIDPP-4i combination therapy as an adjuvant treatment strategy to enhance the efficacy of novel beta-cell replacement therapies for T1D. In this regard, we discuss the potential immune and metabolic mechanisms through which vitamin D and DPP-4 inhibitors can promote the long-term function and survival of transplanted islets in patients with T1D receiving various types of beta-cell replacement therapies, including therapeutic approaches using encapsulated stem cell-derived beta cells. Full article

Despite its value as a culinary, medicinal, and essential oil crop, caraway struggles to grow and develop its biochemical quality in drought-prone sandy soils. To tackle this challenge, we conducted two field trials under drip irrigation, testing four rates of organic manure (0, 5, 10, and 15 ton/hectare (ha) and three foliar biostimulants: vitamin B₁ (50 and 100 mg L⁻¹), vitamin E (50 and 100 mg L⁻¹), and active yeast (100 and 150 mL L⁻¹). We used a randomized split-plot design with three replicates, assigning manure rates to main plots and biostimulants to subplots. We measured plant height, stem diameter, branch number, dry biomass, umbels per plant, 1000-seed weight, seed yield (per plant and per ha), essential oil content, chlorophyll a and b, carotenoids, and leaf N, P, and K. All treatments outperformed the unfertilized control. Applying 15 ton/ha of manure alone increased mean plant height by 185.3 cm, stem diameter by 2.93 mm, branch number by 14.5, and herbal weight by 91.97 g across both seasons—a gain of about 11–15%. Foliar application of vitamin B₁ at 100 mg L⁻¹ (without manure) achieved even larger gains: mean plant height improved by 176.5 cm, stem diameter by 2.6 mm, branches number by 15.1, and herbal biomass by 103.95 g (20–36% growth increases). It also boosted essential oil yield by 1.89 mL per plant (16–50%) and enhanced nutrient uptake. The most pronounced synergy emerged when combining 15 ton/ha of manure with 100 mg L⁻¹ vitamin B₁, raising seed yield to 1698.8 kg/ha (35%), plant height to 184.7 cm (52%), number of branches to 17.4 per plant (56%), umbels to 38.1 per plant (42%), 1000-seed weight to 16.9 g (48%), and essential oil yield to 2.3 mL per plant (115%), compared to the control. Chlorophyll a increased by 50%, chlorophyll b by 33%, carotenoids by 35%, and leaf N, P, and K by 43%, 90%, and 76%, respectively. Manure combined with vitamin E or yeast delivered moderate improvements. These findings demonstrate that integrating organic manure with targeted foliar biostimulants—especially vitamin B₁—under drip irrigation, is a sustainable strategy to maximize caraway yield, oil content, and nutritional quality on marginal sandy soils. Full article

This study conducts a detailed analysis of cybersecurity threats, including artificial intelligence (AI)-driven cyber-attacks targeting vehicle-to-vehicle (V2V) and electric vehicle (EV) communications within the rapidly evolving field of connected and autonomous vehicles (CAVs). As autonomous and electric vehicles become increasingly integrated into daily life, their susceptibility to cyber threats such as replay, jamming, spoofing, and denial-of-service (DoS) attacks necessitates the development of robust cybersecurity measures. Additionally, EV-specific threats, including battery management system (BMS) exploitation and compromised charging interfaces, introduce distinct vulnerabilities requiring specialized attention. This research proposes a comprehensive and integrated cybersecurity framework that rigorously examines current V2V, vehicle-to-everything (V2X), and EV-specific systems through systematic threat assessments, vulnerability analyses, and the deployment of advanced security controls. Unlike previous state-of-the-art approaches, which primarily focus on isolated threats or specific components such as V2V protocols, the proposed framework provides a holistic cybersecurity strategy addressing the entire communication stack, EV subsystems, and incorporates AI-driven threat detection mechanisms. This comprehensive and integrated approach addresses critical gaps found in the existing literature, making it significantly more adaptable and resilient against evolving cyber-attacks. Our framework aligns with industry standards and regulatory requirements, significantly enhancing the security, safety, and reliability of modern transportation systems. By incorporating specialized cryptographic techniques, secure protocols, and continuous monitoring mechanisms, the proposed approach ensures robust protection against sophisticated cyber threats, thereby safeguarding vehicle operations and user privacy. Full article

Lead (Pb) and cadmium (Cd) severely impair rice growth, yield, and grain quality. This study assessed the role of exogenous gamma-aminobutyric acid (GABA) in mitigating Pb and Cd toxicity in aromatic rice ‘Guixiangzhan’. Treatments included the control (no Pb, Cd, or GABA), GABA (1 mM), Pb (800 mg/kg of soil)+GABA, Cd (75 mg/kg of soil)+GABA, Pb+Cd+GABA, Pb, Cd, and Pb+Cd without GABA. GABA improved chlorophyll and carotenoid, protein, proline and GABA contents whilst reducing oxidative stress under Pb/Cd toxicity. GABA application regulated antioxidant enzyme activities, net photosynthesis, and gas exchange, while its effects on nitrate reductase and glutamine synthetase were variable. Compared with Pb+Cd, the grain yields were 34.03%, 31.94%, 15.88%, 24.86%, and 17.32% higher in (Pb, Cd, Pb+Cd)+GABA, Pb, and Cd treatments, respectively. Furthermore, GABA reduced Pb and Cd accumulation in aboveground parts, while Ca, Mg, Fe, Cu, Zn, and Mn levels varied across treatments. Cd translocation was more from root-to-leaves, while Pb translocation was more from leaves-to-grains. Grain Pb and Cd positively correlated with their root, stem, and leaf contents but negatively with mineral nutrients. Overall, exogenous GABA mitigated Pb and Cd toxicity in aromatic rice. Full article

In recent years, an increasing amount of research has investigated the impact of chronic inflammation on the development and progression of both neurological and psychiatric disorders, including epilepsy, depression, schizophrenia, and bipolar disorder. Moreover, growing attention is being paid to how inflammatory processes contribute to disease mechanisms, influence symptom severity, and interact with pharmacological treatments in these conditions. Changes in the levels of inflammatory biomarkers, such as cytokines and C-reactive protein, may signal the early stages of neurological disorder development. Furthermore, specific biomarker profiles have been identified for individual diseases, and chronic treatment may affect their blood levels. Over the last two decades, significant progress in the study of inflammatory biomarkers in psychiatric disorders and epilepsy has been achieved, demonstrating an association between biomarkers with symptoms, a potential prognostic role, and possible use in personalising therapy. Furthermore, widely used methods for biomarker evaluation, such as immunoenzymatic assays and flow cytometry, remain essential tools for current research. Despite numerous indications of the importance of inflammation in psychiatry and neurology, the available studies are characterised by considerable heterogeneity in terms of both population selection and methodology. Based on the available data, inflammatory biomarkers represent a promising diagnostic and therapeutic tool for epilepsy and psychiatric disorders. Although existing studies suggest a correlation between inflammation and the symptoms of various disorders, inconsistent results highlight the need for further research to enable wider implementation of these findings in psychiatric and epilepsy practice. Advancing knowledge of inflammatory biomarkers is essential for improving treatment outcomes and promoting the development of targeted interventions. Full article

This study aimed to develop an effective method to overcome the challenge of straw return in cold-region soil. We systematically investigated the synergistic mechanism of montmorillonite (MMT) and composite amino acid (CAA) on straw humification and carbon sequestration through a low-temperature litterbag field experiment. The results indicate that the combined treatment (MMT-CAA) significantly increased the decomposition rate of straw by 42.1% compared to the control (CK), with MMT showing particular efficacy in lignin degradation (28.3% reduction), while the CAA preferentially decomposed cellulose (19.7% reduction). An FTIR analysis of the decomposition products confirmed these findings. Water-soluble organic carbon (WEOC) and its three-dimensional fluorescence spectra exhibited a 25.0% increase in MMT-CAA and enhanced aromaticity of humic acid-like substances. Humic substances and their ¹³C-NMR revealed that MMT-CAA enhanced humic acid formation and molecular stability by 31.4% (with a 47.8% increase in aromaticity). A further redundancy analysis and symbiotic network of microorganisms demonstrated that MMT-CAA increased the abundance of lignocellulose-degrading phyla (Actinomycetes and Stramenomycetes) and the formation of a complex co-degradation network. Field corn planting trials indicated that MMT-CAA increased plant height by 55.1%, stem thickness by 58.7%, leaf area by 70.2%, and the SPAD value by 41.1%. Additionally, MMT significantly reduced CO₂ and N₂O emission fluxes by 35.6% and 15.8%, respectively, while MMT-CAA increased CH₄ uptake fluxes by 13.4%. This study presents an innovative strategy, providing mechanistic insights and practical solutions to synergistically address the challenges of slow straw decomposition and carbon loss in cold regions. Full article

This study provides a comprehensive assessment of the population structures, anatomical adaptations, and chloroplast genome organizations of three rare tree species—Fraxinus sogdiana Bunge, Celtis caucasica Willd., and Betula jarmolenkoana Golosk.—from the Northern Tien Shan region of Kazakhstan. Field surveys revealed species-specific demographic patterns, with F. sogdiana and B. jarmolenkoana populations displaying a complete age spectrum and signs of ongoing regeneration, while C. caucasica exhibited a lack of juvenile stages, indicating regeneration failure. Anatomical analysis of leaf and stem tissues highlighted adaptive features aligned with habitat conditions: F. sogdiana showed mesophytic traits suited for riparian environments, C. caucasica displayed xeromorphic structures reflecting drought tolerance, and B. jarmolenkoana demonstrated structural reinforcement adapted to high-altitude stressors. Whole chloroplast genome sequencing revealed conserved quadripartite architecture across species, with minor variations in gene content and inverted repeat boundaries suggesting lineage-specific evolution. The findings underscore the ecological sensitivity and conservation priority of these species and provide foundational data for future ecological monitoring, restoration efforts, and phylogenomic research in Central Asian montane ecosystems. Full article

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting BCSCs and expands on the challenges for the development of anti-BCSC drugs. We explore cutting-edge approaches like artificial intelligence (AI)-driven drug discovery and urge readers to seriously consider biological clocks and chronotherapy as experimental variables in drug discovery. Collectively, the task of cancer researchers is to overcome the many hurdles targeting BCSCs if we hope to tangibly improve breast cancer treatment outcomes and reduce mortality. Full article

VEXAS syndrome (Vacuoles, E1-enzyme, X-linked, Autoinflammation, and Somatic) is a recently identified late-onset autoinflammatory disorder characterized by a unique interplay between hematological and inflammatory manifestations. It results from somatic mutations in the UBA1 gene, located on the short arm of the X chromosome. Initially, females were considered mere carriers, with the syndrome primarily affecting males over 50. However, recent evidence indicates that heterozygous females can exhibit symptoms as severe as those seen in hemizygous males. The disease manifests as systemic inflammation, macrocytic anemia, thrombocytopenia, chondritis, neutrophilic dermatoses, and steroid-dependent inflammatory symptoms. Due to its overlap with autoimmune and hematologic disorders such as relapsing polychondritis, Still’s disease, and myelodysplastic syndromes, misdiagnosis is common. At the molecular level, VEXAS syndrome is driven by impaired ubiquitination pathways, resulting in dysregulated immune responses and clonal hematopoiesis. A key diagnostic marker is the presence of cytoplasmic vacuoles in myeloid and erythroid precursors, though definitive diagnosis requires genetic testing for UBA1 mutations. Traditional immunosuppressants and TNF inhibitors are generally ineffective, while JAK inhibitors and IL-6 blockade provide partial symptom control. Azacitidine and decitabine have shown promise in reducing disease burden, but hematopoietic stem cell transplantation (HSCT) remains the only curative treatment, albeit with significant risks. This review provides a comprehensive analysis of VEXAS syndrome, examining its clinical features, differential diagnoses, diagnostic challenges, and treatment approaches, including both pharmacological and non-pharmacological strategies. By enhancing clinical awareness and optimizing therapeutic interventions, this article aims to bridge emerging genetic insights with practical patient management, ultimately improving outcomes for those affected by this complex and often life-threatening disease. Full article