Search Results (2,229)

Epigenetic regulation, particularly DNA methylation, plays a crucial role in plant adaptation to environmental stresses by modulating gene expression without altering the underlying DNA sequence. In response to major abiotic stresses such as salinity, drought, heat, cold, and heavy metal toxicity, plants undergo dynamic changes in DNA methylation patterns. These modifications are orchestrated by DNA methyltransferases and demethylases with variations depending on plant species, genetic background, and ontogenic phase. DNA methylation affects the expression of key genes involved in cellular, physiological, and metabolic processes essential for stress tolerance. Furthermore, it contributes to the establishment of stress memory, which can be transmitted across generations, thereby enhancing long-term plant resilience. The interaction of DNA methylation with other epigenetic mechanisms, including histone modifications, small RNAs, and chromatin remodeling, adds layers of regulatory complexity. Recent discoveries concerning N6-methyladenine have opened new avenues for understanding the epigenetic landscape in plant responses to abiotic stress. Overall, this review addresses the central role of DNA methylation in regulating plant stress responses and emphasizes its potential for application in crop improvement through epigenetic and advanced biotechnological approaches. Full article

Soil salinity severely impairs crop productivity by inducing osmotic stress, ionic toxicity, and oxidative damage. This study investigated the mechanisms by which foliar-applied wood vinegar (WV), a biomass pyrolysis byproduct rich in organic acids and minerals, alleviates salt stress (100 mM NaCl) in hydroponically grown wheat (Triticum aestivum L.). Three WV dilutions (100×, 300×, 500×) were tested to evaluate their effects on growth, antioxidant systems, chlorophyll metabolism, and ion homeostasis. The results demonstrated that 300×-diluted WV (WV3) most effectively mitigated salt stress, increasing shoot biomass by 81% and root length by 75% compared to salt-stressed controls. WV3 restored antioxidant enzyme activities to non-stressed levels, reduced lipid peroxidation, and normalized chlorophyll overaccumulation induced by salinity. Elemental profiling revealed that WV3 enhanced shoot K⁺ and Ca²⁺ uptake while reducing Na⁺ accumulation, thereby improving ion homeostasis. Additionally, WV3 promoted Fe translocation to shoots, supporting chlorophyll synthesis. However, 100× WV (WV1) exhibited phytotoxicity due to excessive organic acids, while 500× (WV5) showed limited efficacy. These findings highlight a 300-fold diluted solution of WV as an optimal dilution for enhancing wheat salt tolerance through coordinated ROS scavenging, photosynthetic protection, and ion regulation. This study provides a scientific basis for integrating WV into sustainable strategies to combat salinity in wheat cultivation. Full article

Background/Objectives: This multicenter retrospective study aims to evaluate the role of Ablative Radiotherapy (RT) in patients with unresectable pleural mesothelioma (PM) who experienced radiological progression after at least one line of chemotherapy, with a maximum involvement of three pleural or extrapleural sites. Methods: Adult patients (≥18 years) with PM treated with stereotactic radiotherapy between 2011 and 2022, limited to a maximum of three pleural or extrapleural sites, were included in the analysis. Ablative RT was required to be administered with radical intent. Endpoints were time to further systemic therapy (TFST), local control (LC), progression-free survival (PFS), overall survival (OS), and acute and late radiotherapy-related toxicity. Results: A total of 56 patients were identified from six Italian and one Swiss radiotherapy center. Treatment was generally well tolerated. Ten patients experienced grade 1 or 2 acute toxicity, while four patients reported persistent chest pain, with one case reaching grade 3 as late toxicity. The median TFST was 18.6 months, with TFST rates of 61.7% and 46.4% at 12 and 24 months, respectively. The median OS was 37.63 months, with 1- and 2-year OS rates of 85.2% and 65.6%. Local control was favorable (79% at 1 year), but most patients experienced disease recurrence outside the SABR treatment volume. The median disease progression-free survival (DPFS) was 8.17 months, with 1- and 2-year DPFS rates of 36% and 19%, respectively. Smoking history correlated with OS and DPFS in univariate analysis, while statistical significance for OS was maintained in multivariate analysis. Additionally, nodal status and PTV volume were associated with OS. Conclusion: SABR is a safe and effective approach for the treatment of oligorecurrent/oligoprogressive PM. The time to further systemic therapy was extended up to 18 months. At two years, 10% of patients remained disease-free, and more than half were alive at three years, suggesting a potentially indolent biological behavior in oligometastatic PM. Full article

Olive mill wastewater (OMW) is a phenol-rich effluent with high organic load, posing significant environmental disposal challenges in the Mediterranean countries. This study evaluated the bioremediation and valorization potential of OMW by eleven edible and/or medicinal fungal strains (Agrocybe cylindracea, Lentinula edodes, Pleurotus sapidus, Pleurotus sajor-caju, Flammulina velutipes, Ganoderma adspersum, Tuber aestivum and Tuber mesentericum). Firstly, screening for mycelial growth on agar media with commercial glucose and OMW (concentrations from 0 to 50%, v/v) revealed a strain-specific tolerance to phenolic toxicity. Although all tested strains could grow on OMW-based media, G. adspersum, T. mesentericum and T. aestivum presented the highest mycelial growth rates (Kr), exceeding 10 mm/day at elevated OMW levels (50%, v/v). Based on screening outcomes, seven strains were selected for further evaluation under static liquid fermentations in media with 15 and 35% (v/v) OMW. Growth kinetics, substrate consumption, phenolic removal, decolorization capacity, intracellular polysaccharide (IPS) and total lipid content were assessed. Tuber spp. and G. adspersum exhibited the highest tolerance to phenolic compounds, producing biomass exceeding 15 g/L at 35%, v/v OMW. Maximum IPS production reached up to 46.23% (w/w), while lipid content exceeded 15% (w/w) of dry biomass in F. velutipes and T. mesentericum, indicating an oleaginous microorganism-like behavior. Phenolic removal surpassed 80% in most cases, demonstrating efficient enzymatic degradation. Decolorization efficiency varied between strains, but remained above 70% for L. edodes, G. adspersum and F. velutipes. These findings highlight the potential of edible and/or medicinal fungi to simultaneously detoxify OMW and produce biomass and high-value metabolites, supporting a sustainable, low-cost agro-industrial waste management aligning with circular bioeconomy principles. Full article

Geogenic contamination of groundwater presents a substantial threat to the enduring production and sustainability of irrigated fruit orchards, especially in arid and semi-arid regions where over 60% of horticultural irrigation depends on groundwater sources. Groundwater quality is increasingly threatened by geogenic contamination, presenting a critical global issue. Geogenic contaminants, such as fluoride and arsenic, combined with agricultural practices and inadequate wastewater treatment, pose a significant threat to groundwater. Concentrations of elements including arsenic, fluoride, boron, iron, and sodium often exceed acceptable thresholds. For instance, arsenic (As) levels up to 0.5 ppm have been reported in parts of South Asia, far exceeding the WHO guidelines limit of 0.01 mg/L. Boron concentrations above 2.0 ppm and fluoride concentrations exceeding 1.5 ppm are prevalent in impacted aquifers. Pollution consequences are far reaching, impacting agricultural ecosystems and human health as polluted water infiltrates the food chain via irrigation. These challenges are compounded by climate change and water scarcity, which further strain water sources, including those used in agriculture. Addressing groundwater contamination requires a multi-faceted approach. Strategies include developing crops that can tolerate toxicants, improving irrigation techniques, and employing advanced wastewater treatment technologies. This study solidifies current knowledge concerning the uptake processes and physiological effects of various pollutants in fruit crops. This review emphasizes the synergistic toxicity of many pollutants, identifies gaps in knowledge in species-specific tolerance, and emphasizes the dearth of comprehensive mitigating frameworks. Potential solutions, such as salt-tolerant rootstocks, gypsum amendments, and alternative irrigation timing, are examined to enhance resilient orchard systems in geogenically challenged areas. Full article

Aluminum (Al) toxicity in acidic soils severely limits the productivity of Chinese fir (Cunninghamia lanceolata) plantations. Despite being a crucial timber species in southern China, the regulatory mechanisms underlying phenolic accumulation and Al tolerance pathways under Al stress in Chinese fir remain unidentified. In this study, 5-month-old Chinese fir seedlings were treated with an exogenous phenolic synthesis inhibitor (AIP) and precursor (MJ) to establish the following groups: CK, AIP, MJ, Al, Al+AIP, and Al+MJ. Physiological and biochemical indicator analyses, transcriptome analysis, and protein interaction network predictions were conducted. The findings revealed that phenolic compounds enhance Al tolerance in Chinese fir through two mechanisms: (1) regulation of active oxygen homeostasis (elevating SOD and POD activities, promoting AsA and GSH accumulation, and augmenting total antioxidant capacity); and (2) modulation of cell wall characteristics (increasing pectin content and pectinase activity, and facilitating Al sequestration in the cell wall). Moreover, MJ was found to synergistically enhance these processes, while AIP impeded them. Genes associated with antioxidant enzymes, secondary metabolite synthesis, and cell wall modification were implicated in the regulatory mechanisms. This study provides a theoretical foundation for elucidating the adaptation of Chinese fir to Al toxicity in acidic soil environments, offers insights for enhancing Chinese fir productivity in acidic soils, and presents a novel target for breeding trees with stress resistance. Full article

Ammonia is a common toxic pollutant in aquaculture environments that poses significant threats to the health, growth, and survival of aquatic organisms. This study investigates the physiological and molecular responses of triploid Crassostrea gigas to ammonia exposure, focusing on the activation and regulation of oxidative stress and immune-related pathways. By integrating histological observations, biochemical assays, and transcriptomic analysis, we systematically revealed the oxidative stress and immune regulatory mechanisms in the hepatopancreas of triploid C. gigas under ammonia exposure. Results showed significant tissue damage in the hepatopancreas, disrupted activities of key antioxidant enzymes including SOD, CAT, and GSH-Px, along with elevated MDA levels, indicating oxidative damage to cellular membrane lipids. Transcriptomic data further indicated significant activation of the glutathione metabolism pathway, with antioxidant genes such as GPX5 and GPX7 displaying a dynamic pattern of initial upregulation followed by downregulation, suggesting their critical roles in modulating oxidative stress responses and maintaining cellular homeostasis. Immunologically, ammonia exposure significantly activated lysosomal and phagosomal pathways, as well as multiple signaling cascades including FOXO, mTOR, and PI3K-Akt. Several key immune regulatory genes exhibited dynamic expression changes, reflecting coordinated regulation of apoptosis, autophagy, and energy metabolism to maintain immune defense and cellular homeostasis. Notably, dynamic expression of the GADD45 gene family in the FOXO signaling pathway underscores the important role of triploid C. gigas in mounting stress responses and adaptive immune regulation under ammonia toxicity. This study provides in-depth molecular insights into the integrated response mechanisms of triploid oysters to ammonia exposure, offering a molecular foundation for understanding bivalve adaptation to ammonia and revealing novel perspectives on molluscan ammonia tolerance. Full article

The efficacy of topical drug delivery via eye drops is often achieved at the expense of tolerability, and consequently, efforts are being made to design strategies that minimize the adverse effects associated with the passage of active pharmaceutical ingredients (APIs) across the ocular surface. Many of these approaches are too complex, costly and challenging to implement on an industrial scale, yet there is increasing evidence that hylan A, a very high molecular weight hyaluronic acid (≥3.0 MDa), may be a promising vehicle for topical drug delivery of ocular therapies. In this review, we explore how the mucoadhesive and viscoelastic properties of eye drop formulations based on hylan A help extend the residence time of APIs at the ocular surface, while maintaining patient comfort. Moreover, we examine how hylan A facilitates the dissolution and stabilization of APIs, as well as their transport across the ocular epithelial barrier, without the need to use toxic penetration enhancers, thereby preserving ocular surface health. Finally, we present evidence indicating that the intrinsic biological properties of hylan A, including its anti-inflammatory effects, help mitigate side effects commonly associated with certain APIs. To illustrate these advantages, we examine the pioneering use of a hylan A-based aqueous eye drop formulation as a vehicle to deliver latanoprost, a prostaglandin analogue widely used in the treatment of glaucoma. This case study demonstrates the potential of hylan A-based eye drops to offer safer and more effective topical drug delivery, especially for long-term ocular therapies where tolerability and biocompatibility are critical. Full article

The therapeutic landscape of adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is undergoing a paradigm shift, driven by the development of immunotherapy-based “chemo-free” and “chemo-light’ regimens. These strategies aim to achieve high efficacy with reduced toxicity, particularly in older adults who may not tolerate intensive chemotherapy. In Philadelphia chromosome-positive (Ph+) BCP-ALL, the incorporation of ABL tyrosine kinase inhibitors (TKIs) with blinatumomab (CD3/CD19 bispecific T-cell engager) has shown remarkable efficacy, with some studies reporting molecular response rates in the range of 90–100% and long-term survival exceeding 80% without the need for intensive chemotherapy or allogeneic hematopoietic cell transplantation (allo-HCT). In Philadelphia-negative (Ph−) BCP- ALL, an immunotherapy-based combination of blinatumomab and inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate) has demonstrated high rates of complete remission and measurable residual disease (MRD) negativity, with manageable toxicity. While chimeric antigen receptor (CAR) T-cell therapy remains a transformative option for relapsed/refractory B-ALL, its integration into frontline treatment is still under investigation. Ongoing trials are evaluating the optimal sequencing and combinations of these agents and their potential to obviate the need for chemotherapy and/or allo-HCT in selected patients. As evidence continues to accumulate, chemo-free and chemo-light regimens, incorporating minimal chemotherapy with targeted agents to balance efficacy and reduced toxicity, are poised to redefine the standard of care for adults BCP-ALL, offering the possibility of durable remissions with reduced treatment-related morbidity. Full article

The treatment of organic phosphate ester (OPE) pollutants in water is a challenging but highly necessary task. In this study, an advanced oxidation process through light activation of peroxymonosulfate (PMS) involving graphene oxide (GO) as a promoter was developed to degrade OPE in water, taking triphenyl phosphate (TPhP) as an example. The developed “Light+PMS+GO” system demonstrated good convenience, high TPhP degradation efficiency, tolerance in a near-neutral pH, satisfactory re-usability, and a low toxicity risk of degradation products. Under the investigated reaction conditions, viz., the full spectrum of a 300 W Xe lamp, PMS of 200 mg L⁻¹, GO of 4 mg L⁻¹, and TPhP of 10 μmol L⁻¹, the “Light+PMS+GO” system achieved nearly 100% TPhP degradation efficiency during a 15 min reaction duration with a 5.81-fold enhancement in the reaction rate constant, compared with the control group without GO. Through quenching experiments and electron paramagnetic resonance studies, singlet oxygen was identified as the main reactive species for TPhP degradation. Further studies implied that GO could accumulate both oxidants and pollutants on the surface, providing additional reaction sites for PMS activation and accelerating electron transfer, which all contributed to the enhancement of TPhP degradation. Finally, the TPhP degradation pathway was proposed and a preliminary toxicity evaluation of degradation intermediates was conducted. The convenience, high removal efficiency, and good re-usability indicates that the developed “Light+PMS+GO” reaction system has great potential for future applications. Full article

Background: Stereotactic body radiation therapy (SBRT) has proven effective in controlling spinal lesions with minimal toxicity, primarily due to its ability to limit spinal cord dose. Recent advances in MR-linac (MRL) technology offer superior spinal cord visualization and real-time gating, which can facilitate dose escalation in spinal tumor treatment while maintaining safety. Purpose: This study aimed to optimize motion management for spine SBRT on an MRL by analyzing patient-specific motion dynamics and evaluating the most effective registration structures. We hypothesized that baseline shifts (BLS) would improve delivery efficiency while maintaining spinal cord dose constraints. The goal was to establish displacement thresholds and assess the role of baseline shift correction adaptative planning in improving treatment delivery efficiency. Methods: Twelve patients underwent two MRI sessions on the MRL. The optimal registration structure was identified, and intrafraction motion was assessed to calculate delivery efficiency. Baseline shift (BLS) simulations were applied for five cases that showed significant motion and suboptimal delivery efficiency, and the dosimetric impact of the BLS was evaluated. The simulated BLS-based plan adaptation was implemented via a segment aperture morphing adapt-to-position workflow. Results: The most stable registration structure was the spinal canal plus three adjacent vertebrae. Cine imaging revealed average intrafraction motion (95th to 5th percentiles) of 0.8 ± 0.5 mm in the right-left (RL) direction, 0.9 ± 0.6 mm in the anterior–posterior (AP) direction, and 0.7 ± 0.5 mm in the SI direction. Simulated BLS improved delivery efficiency to >80% in all but one case, with a ±1 mm displacement threshold tolerance. While target coverage remained consistent after BLS simulation, the spinal cord dose increased by 7–60%, exceeding the 14 Gy constraint in three of the five simulated cases. Conclusions: Cine imaging and BLS can enhance delivery efficiency in spine SBRT but may increase spinal cord dose. These findings underscore the need for careful patient selection, advanced motion management, and patient-specific BLS protocols. Full article

As chemical messengers, phytohormones can enhance the tolerance of plants to stress caused by toxic elements (TEs) such as cadmium (Cd), lead (Pb), and zinc (Zn). This study investigated the combined toxicity of Cd, Pb, and Zn, and its impact on stress phytohormones (jasmonates, salicylic acid, and abscisic acid), in oat (Avena sativa L.) using anthropogenically contaminated soil in a 4-week pot experiment. The uptake of TEs by the roots increased in the multi-contaminated soil, while Zn was the only TE to be translocated to the leaves. The toxic effect of the TEs was assessed in terms of plant growth, revealing a decline in leaf dry biomass, whereas the impact on the roots was insignificant. These findings align with the levels of stress phytohormones. An increase in bioactive forms of stress phytohormones in leaves due to TEs indicates TE toxicity and leaf sensitivity. Conversely, low levels of these phytohormones, along with crosstalk between them, suggest reduced defense against TEs in the roots. The abundance of stress phytohormones declined in the following order: salicylic acid > jasmonates > abscisic acid. These results help to understand the mechanism by which plants respond to TEs, particularly their combined toxicity. Full article

Plants are constantly exposed to various environmental challenges, such as drought, flooding, heavy metal toxicity, and pathogen attacks. To cope with these stresses, they employ several adaptive strategies. This review highlights the potential of plant-derived smoke (PDS) solution as a natural biostimulant for improving plant health and resilience, contributing to both crop productivity and ecological restoration under abiotic and biotic stress conditions. Mitigating effects of PDS solution against various stresses were observed at morphological, physiological, and molecular levels in plants. PDS solution application involves strengthening the cell membrane by minimizing electrolyte leakage, which enhances cell membrane stability and stomatal conductance. The increased reactive-oxygen species were managed by the activation of the antioxidant system including ascorbate peroxidase, superoxide dismutase, and catalase to meet oxidative damage caused by challenging conditions imposed by flooding, drought, and heavy metal stress. PDS solution along with other by-products of fire, such as charred organic matter and ash, can enrich the soil by slightly increasing its pH and improving nutrient availability. Additionally, some studies indicated that PDS solution may influence phytohormonal pathways, particularly auxins and gibberellic acids, which can contribute to root development and enhance symbiotic interactions with soil microbes, including mycorrhizal fungi. These combined effects may support overall plant growth, though the extent of PDS contribution may vary depending on species and environmental conditions. This boost in plant growth contributes to protecting the plants against pathogens, which shows the role of PDS in enduring biotic stress. Collectively, PDS solution mitigates stress tolerance in plants via multifaceted changes, including the regulation of physico-chemical responses, enhancement of the antioxidant system, modulation of heavy metal speciation, and key adjustments of photosynthesis, respiration, cell membrane transport, and the antioxidant system at genomic/proteomic levels. This review focuses on the role of PDS solution in fortifying plants against environmental stresses. It is suggested that PDS solution, which already has been determined to be a biostimulant, has potential for the revival of plant growth and soil ecosystem under abiotic and biotic stresses. Full article

Chlorophyll, the green pigment essential for photosynthesis, abundantly found in green vegetables and algae, has attracted growing scientific interest for its potential therapeutic effects, particularly in diabetes management. Recent research highlighted that chlorophyll and its derivatives may beneficially influence glucose metabolism and oxidative stress, key factors in diabetes. This review examines current knowledge on how chlorophyll compounds could aid diabetes control. Chlorophyll and its derivatives appear to support glucose regulation primarily through actions in the gastrointestinal tract. They modulate gut microbiota, improve glucose tolerance, reduce inflammation, and alleviate obesity-related markers. While chlorophyll itself does not directly inhibit digestive enzymes like α-glucosidase, its derivatives such as pheophorbide a, pheophytin a, and pyropheophytin a may slow carbohydrate digestion, acting as α-amylase and α-glucosidase inhibitors, reducing postprandial glucose spikes. Additionally, chlorophyll enhances resistant starch content, further controlling glucose absorption. Beyond digestion, chlorophyll derivatives show promise in inhibiting glycation processes, improving insulin sensitivity through nuclear receptor modulation, and lowering oxidative stress. However, some compounds pose risks due to photosensitizing effects and toxicity, warranting careful consideration. Chlorophyllin, a stable semi-synthetic derivative, also shows potential in improving glucose and lipid metabolism. Notably, pheophorbide a demonstrates insulin-mimetic activity by stimulating glucose uptake via glucose transporters, offering a novel therapeutic avenue. Overall, the antioxidant, anti-inflammatory, and insulin-mimicking properties of chlorophyll derivatives suggest a multifaceted approach to diabetes management. While promising, these findings require further clinical validation to establish effective therapeutic applications. Full article

Titanium, the second most abundant and one of the cheapest, non-toxic transition metals in the Earth’s crust, is highly favorable for catalytic applications due to its widespread availability, low cost, low toxicity, and well-documented biocompatibility. However, because of its high affinity for oxygen and inherent Lewis acidity, titanium complexes generally exhibit lower tolerance toward various functional groups compared with complexes of later transition metals. The incorporation of cyclopentadienyl ligands significantly enhances the structural tunability of these complexes in their 3D configuration. By modifying the ligand framework, it is possible to fine-tune the Lewis acidity of the central titanium atom as well as the lability and binding characteristics of the ligands. This strategy enables precise control over the catalytic performance of titanocene complexes. The main body of this review provides an overview of recent advances in titanocene catalysis within the field of chemical synthesis since 2019. It includes illustrative examples that demonstrate the substrate scope and practical applications of titanocene catalysts in the synthesis of complex organic molecules and natural products. Finally, the review outlines current research opportunities and strategic directions for future developments in titanocene-based catalysis. Full article