Search Results (1,077)

Neuroinflammation plays a central role in the onset and progression of neurodegenerative disorders. Several disease-modifying therapies have been developed to target neuroinflammatory pathways in specific disorders. However, their ability to stop disease progression or restore neuronal and mitochondrial homeostasis remains limited. This is still a major unmet clinical need. In this context, mesenchymal stromal cell (MSC)-derived Extracellular Vesicles (EVs) have emerged as a promising cell-free therapeutic strategy due to their ability to modulate immune responses and promote neuroprotection through the delivery of bioactive cargo. Recent evidence has identified a distinct subset of EVs, known as mitochondrial EVs (mito-EVs), which carry mitochondrial DNA, proteins, and functional components. These vesicles may uniquely influence cellular bioenergetics, redox balance, and neuroinflammatory signaling, offering additional therapeutic potential compared to conventional MSC-EVs. This review summarizes the role of MSC-derived EVs in neuroinflammatory disorders, with a particular focus on mito-EVs. It also discusses preconditioning strategies to enhance EV efficacy, including hypoxic, inflammatory, pharmacological priming and genetic engineering approaches. Finally, we critically evaluate current preclinical evidence regarding the treatment of major neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis, as well as Traumatic Injury, highlighting the key challenges for clinical translation. Full article

This study presents a validation-aware EEG framework based on Chaotic Pattern of Prime Numbers (CPPN) features for depression treatment-response modelling across one SSRI cohort and two rTMS cohorts. CPPN features were evaluated through a seven-protocol validation hierarchy spanning random segment splitting, segment-level cross-validation, nested segment-level cross-validation, leave-N-subjects-out, fixed-feature leave-one-subject-out (LOSO), nested leave-N-subjects-out, and nested LOSO, with normalisation, NCA ranking, feature-count selection where applicable, and model fitting confined to the appropriate training partitions. In the representative K-nearest neighbour (KNN) comparison, segment-level 10-fold CV achieved accuracies of 98.79% for Mumtaz SSRI, 99.32% for small Atieh rTMS, and 99.42% for big Atieh rTMS, demonstrating strong discriminative structure in the CPPN feature space. In the available segment-level KNN comparison, CPPN features with fold-internal NCA-selected feature sets exceeded conventional statistical EEG features by 29.53, 16.33, and 11.45 percentage points across the three cohorts. Subject-wise validation produced lower and more cohort-dependent estimates, with the best fixed-feature LOSO accuracy of 80.00% and the best nested LOSO accuracy of 73.33% in the small Atieh rTMS cohort. These results show that CPPN provides a compact, inspectable and computationally accessible EEG feature representation, while the validation hierarchy gives a transparent account of how performance changes from segment-level separability to held-out-subject evaluation. The main contribution is methodological: this study combines an original CPPN feature representation with explicit validation-depth analysis, leakage-aware feature selection, and interpretable channel/bin inspection. It therefore provides a rigorous basis for future externally validated EEG treatment-response studies without claiming prospective clinical deployment from the present retrospective cohorts. Full article

Abiotic stresses limit crop productivity by disrupting water relations, carbon assimilation, nutrient acquisition, membrane stability, and redox homeostasis. Partial root-zone irrigation (PRI), commonly implemented as partial root-zone drying (PRD), is often viewed as a deficit-irrigation strategy to improve water-use efficiency; however, this view underestimates the biological consequences of spatial root-zone heterogeneity. This review evaluates PRI as a spatially structured, priming-like framework for crop adaptation to abiotic stress. Available evidence indicates that localized drying and wet-side water uptake can coordinate root sensing, hydraulic–chemical signaling, abscisic acid delivery, hormone crosstalk, xylem-mediated regulation, and stomatal control. Beyond gas exchange, PRI is associated with photosynthetic maintenance, osmotic adjustment, antioxidant and redox regulation, root architectural plasticity, nutrient acquisition, and metabolic reprogramming. Evidence is strongest for drought, whereas responses to low temperature, salinity, heat-associated evaporative demand, and combined stresses remain more context-dependent. Emerging work also links PRI to rhizosphere restructuring and microbiome shifts, but the causal mechanisms and field reproducibility remain unresolved. We argue that future progress requires matched PRI–deficit-irrigation comparisons, standardized switching thresholds, shared physiological and molecular readouts across crops, high-resolution root biology, and commercially realistic field validation. This framing distinguishes conserved physiological outcomes from mechanisms that may differ among crops, genotypes, and irrigation designs. Full article

Melatonin has been recognized as a regulator of plant growth and stress responses; however, its role in nitrogen metabolism, particularly in Capsicum chinense Jacq., remains poorly understood. In this study, we evaluated the effect of melatonin priming alone (chemopriming, CP) or in combination with substrate reinforcement (soil drench, SD) (CP + SD), at different doses, on physiological, biochemical, and molecular parameters in habanero pepper plants growing in non-stressed conditions. Growth traits, nitrogen-related metabolites, total carbohydrates, the expression of key genes involved in nitrogen metabolism, and glutamate dehydrogenase (GDH) activity were analyzed. The results showed that priming increased biomass mainly at 25 and 50 µM, whereas the combined treatment promoted improvements from early doses (5 µM). Additionally, the evaluated genes exhibited tissue-specific expression patterns. Most genes were downregulated in leaves, whereas proline and total carbohydrate levels correlated with fresh and dry weight. Our results provide new insights into the regulation of nitrogen metabolism according to the application method and dosage, establishing an application strategy to optimize nitrogen metabolism and growth in habanero peppers. The mechanism of melatonin in regulating the balance of C and N metabolites and its impact on the response of chili plants to growth and environmental signals should be addressed later. Full article

Lunar lava tubes are subsurface cavities generated by volcanic activity and are regarded as promising targets for exploration because they can offer natural shielding and potentially support future lunar infrastructures as protected shelters and scientific laboratories. Autonomous navigation in these environments remains challenging due to the absence of illumination, sparse or repetitive geometric features, uneven terrain, and intermittent communications that limit teleoperation. In this framework, the Italian Space Agency (ASI) is pursuing a dedicated mission, and OHB Italia has been appointed the prime contractor to perform a candidate system-architecture study for lava tube exploration. This paper presents the activities and results related to the definition of the subsurface Guidance, Navigation, and Control (GNC) algorithm for a rover/hopper system. To address the above constraints, this study investigates the requirements for autonomous onboard navigation, focusing on sensor selection for Simultaneous Localization and Mapping (SLAM) as a fundamental prerequisite for mission success. A weighted-criteria evaluation framework is developed to assess various sensing modalities, considering mission-specific constraints. Based on this analysis, a sensor configuration optimized for GPS-denied and unilluminated environments is proposed. The effectiveness of the selected sensing architecture is validated through a simulation campaign conducted in simulation environments (CoppeliaSim v4.10.0/MATLAB 2025a), using two representative SLAM pipelines (ICP and LOAM) in LiDAR-only and LiDAR + IMU configurations. Finally, a modular Guidance, Navigation, and Control (GNC) architecture incorporating frontier-based exploration is proposed. Full article

Premature ovarian insufficiency (POI) is a heterogeneous disorder, and cyclophosphamide (CTX)-induced ovarian injury represents an acquired POI-like condition rather than the full clinical spectrum of POI. In this study, CTX was used to establish a granulosa cell dysfunction model to evaluate whether primed avian mesenchymal stem cell-derived small extracellular vesicles (primed AMSC-sEVs) could restore granulosa cell homeostasis under human menopausal gonadotropin (hMG) stimulation, a clinically relevant gonadotropin context used in ovarian stimulation. Human granulosa cells were exposed to CTX and subsequently treated with hMG, naïve AMSC-sEVs, or primed AMSC-sEVs. Cell viability, mitochondrial membrane potential, AMH and FSHR expression, and hormone secretion were examined. CTX reduced cell viability, mitochondrial membrane potential, AMH and FSHR expression, and AMH/estradiol secretion, confirming the establishment of a POI-like granulosa cell dysfunction state. hMG partially restored selected functional markers but showed limited effects on cell viability and mitochondrial recovery. In contrast, primed AMSC-sEVs markedly restored granulosa cell viability, mitochondrial membrane potential, AMH and FSHR expression, and endocrine output, with stronger effects than naïve AMSC-sEVs. Co-treatment with hMG did not consistently enhance the restorative effects of primed AMSC-sEVs beyond those achieved by primed AMSC-sEVs alone. These findings indicate that primed AMSC-sEVs primarily act by restoring granulosa cell and mitochondrial homeostasis, thereby supporting the cellular competence required for gonadotropin responsiveness in an acquired POI-like condition. Full article

Background: Cocaine use disorder (CUD) remains a major global health concern, with no FDA-approved pharmacological treatments currently available. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has shown promising preclinical effects in disrupting the consolidation and retrieval of drug-associated memories, thereby attenuating relapse-like behaviors. Objectives: The present study evaluated the effects of a low-THC CBD-rich cannabis extract (NPCE) on the reinstatement and reconsolidation of cocaine-induced conditioned place preference (CPP) in male CD1 (ICR) mice, an approach not previously investigated. Methods: The extract was administered at a dose equivalent to 20 mg/kg of CBD. Treatment significantly attenuated both priming- and stress-induced reinstatement of cocaine-induced CPP. Reinstatement was triggered either by a cocaine priming injection or by acute stress exposure, whereas reconsolidation-like processes were assessed by administering the extract following memory reactivation sessions and subsequently evaluating the persistence of cocaine-associated preference over time. Results: NPCE showed a consistent result with disruption of reconsolidation-like processes of cocaine-associated memory, with effects persisting for at least two weeks. The extract alone did not induce conditioned preference or aversion. Conclusions: These findings suggest that NPCE modulates drug-associated memory processes involved in relapse-like behavior. However, the underlying mechanisms were not directly evaluated and remain to be elucidated. Further studies are warranted to include both sexes, evaluate effects across multiple behavioral paradigms, directly compare full-spectrum extracts with isolated cannabinoids, and incorporate receptor-specific approaches to clarify the mechanisms of action. Full article

To address the lack of a commercially available vaccine for goose circovirus (GoCV), we developed and evaluated a prokaryotically expressed subunit vaccine targeting the viral capsid (Cap) protein. A truncated Cap protein (GoCV-ΔCap) was expressed in Escherichia coli (E. coli) and formulated with aluminum hydroxide as a subunit vaccine (GoCVsubvac). Goslings were primed intramuscularly (i.m.) with high (75 µg) or low (15 µg) doses GoCVsubvac, followed by a boost 14 days later. At 14 days post-boost, goslings were challenged with GoCV and were administered a bivalent inactivated vaccine against Newcastle disease virus (NDV) and H9-subtype Avian influenza virus (AIV). Using our established gosling pathogenicity model, vaccine efficacy was evaluated via body weight, lesions, viral load, antibody titers, cytokine responses, and interference with NDV/AIV immunity. Results demonstrated that the GoCV-ΔCap vaccine, especially the high-dose formulation, provided effective immunoprotection. It elicited robust humoral and cellular immune responses, reduced lymphoid pathology, and decreased the viral detection rate in lymphoid tissues from 100% (5/5) in infected controls to 40% (2/5). Importantly, it alleviated GoCV-induced immunosuppression and preserved the immunogenicity of co-administered vaccines. This novel subunit vaccine is a promising candidate for controlling GoCV disease (GoCVD). Full article

This study evaluated the effects of polyethylene glycol concentrations in enhancing the physiological performance of the rice varieties and their recovery ability after drought stress. The experiment comprised of IR64, NIL-SUB1DRO1, and NIL-DRO1. Seed priming was conducted by submerging 5 g of samples in petri dishes containing 100 mL of 5% and 10% PEG solutions. Drought stress significantly reduced all the growth traits, with the susceptible genotypes IR64 recorded highest reduction of shoot length 36%, tiller number 41.3%, shoot dry weight 77%, and root dry weight 72% compared to non-primed NIL-DRO1 and NIL-SUB1DRO1 with reduction in shoot length 34–35%, tiller number 34–45%, root dry weight 60–66%, and shoot dry weight (70–71%). Similar results were recorded for IR64, Pn, 63%, gs 78% E 66%, and RWC 66%, respectively, compared with NIL-DRO1 (55%, 60%, and 58%), while NIL-SUB1DRO1 showed reductions of 55%, 50%, and 54%. PEG 5% and 10% significantly enhanced primed IR64 Pn (29–57%), gs (70%), E (56–64%), and RWC 65%. During the recovery phase, primed seedlings showed a more rapid restoration of growth and photosynthetic efficiency than the non-primed seedlings. PEG 5% and 10% were effective in mitigating drought stress and enhanced recovery ability of rice. Full article

Background/Objectives: The Supplemental Nutrition Assistance Program (SNAP) is the largest food assistance program in the United States providing income-eligible households with cash-like assistance to spend on food. In October 2021, a historic policy change permanently increased benefit amounts by 21 percent. This study assessed differences in diet quality and food security, supplemented by participant descriptions of using SNAP, among adults with low incomes residing in the state of Massachusetts from before (October 2020–January 2021) to after (December 2021–February 2022) the benefit increases. Methods: Derived from The Greater Boston Food Bank’s Annual Statewide Survey, our sample included adults with household incomes ≤300% of the federal poverty level who completed diet and food security measures. We calculated Prime Diet Quality Scores (PDQSs), with higher scores reflecting more nutritious diets on a scale of 0–70. Adjusted difference-in-difference regression models evaluated differences in PDQS and food security between SNAP participants and non-participants from before to after the benefit increases. Reflexive thematic analysis of write-in responses summarized experiences with SNAP. Results: Complete data were available for 1051 respondents before and 801 respondents after SNAP benefit increases. We found no significant differences in diet quality or household food security for SNAP participants, compared to non-participants, from before to after the benefit increases. In write-in comments, respondents expressed gratitude for increased benefits but also fear of them being rescinded. Increased benefits helped some better meet food needs, yet many noted rising costs of living prevented benefits from stretching as far. Conclusions: Increased SNAP benefits did not impact food security or diet quality among this sample. SNAP benefits may need to be further increased to meet the nutritional needs of families. Full article

Seed priming is recognized as an environmentally friendly technique to enhance the physiological and biochemical performance of crops. However, its effectiveness varies depending on factors such as crop type, priming agents and climatic conditions. Based on this hypothesis, this comparative, climate- and soil-dependent meta-synthesis study therefore aimed to evaluate how these factors shape plant responses in common bean (Phaseolus vulgaris L.) and soybean (Glycine max L.), while providing insights into sustainable strategies for improving crop performance, food security, and progress toward sustainable development goals. A cross-study synthesis of 31 peer-reviewed articles from Web of Science, Scopus, and Google Scholar evaluated the influence of these factors on key physiological traits, chlorophyll content (CC) and net photosynthesis rate (Pn), and biochemical traits, proline (Pro), superoxide dismutase (SOD), and catalase (CAT) activity. The findings indicated greater priming-induced enhancements in common bean than soybean for most traits: chlorophyll content (36.6% in common bean and 25.6% in soybean), net photosynthesis rate (33.2% in common bean and 19.8% in soybean), proline content (45.2% in common bean and 40.9% in soybean), and SOD activity (37.1% in common bean and 30.5% in soybean). Soybean only showed superior enhancement in CAT activity (40.1% in soybean and 19.5% in common bean). The climatic conditions impacted the outcomes, with physiological traits (CC and Pn) responding more prominently under semi-arid and arid climates, and biochemical traits (Pro, CAT and SOD) showing higher responsiveness in continental and Mediterranean climates. Significant (p < 0.05) correlations were found between CAT activity and priming agents (r = 0.54); SOD and crop type (r = 0.52); and Pn and crop type (0.90). Multivariate analysis revealed that soybean was positively associated with silt, clay, pH, tropical climate and CAT activity, while common bean was linked to nitrogen, arid conditions, SOD activity and proline. These differences could be due to the molecular and genetic variations in the two crops. Unlike previous reviews, this study provides the first quantitative synthesis integrating crop type, priming agents, and climatic variables, aiming to evaluate how these factors influence the responses of two major legume crops to seed priming. Overall, the findings highlight the need for crop- and environment-specific priming protocols to optimize the benefits of seed priming as a cost-effective approach to enhance crop performance and productivity. Full article

Effective and sustainable control strategies for pine wilt disease, caused by the pine wood nematode (Bursaphelenchus xylophilus), are urgently needed, as reliance on conventional chemical nematicides faces increasing limitations. In this study, a new kind of integrated approach is proposed. It pairs microbial fermentation filtrates with the green chemicals arecoline and sodium silicate. The filtrates were obtained from bacterial and fungal strains that were had isolated from Pinus massoniana rhizosphere soil. The nematicidal efficacy of individual and combined treatments was evaluated in vitro, while their ability to induce systemic resistance in P. massoniana seedlings was assessed through defense enzyme assays, malondialdehyde (MDA) content measurement, and defense-related gene expression analysis. Results identified several highly effective combinations, particularly arecoline plus CSZ33 and sodium silicate plus CSUFT-F23, which achieved over 72% control efficacy. These formulations not only showed direct toxicity but also significantly enhanced the plant’s antioxidant capacity and upregulated key defense genes. Furthermore, untargeted metabolomics linked these effects to specific bioactive metabolites in the fermentation filtrates, such as D-glutamic acid. This work demonstrates that hybrid bio-chemical formulations can successfully merge immediate pathogen suppression with long-term host resistance priming, offering a promising, sustainable strategy for the integrated management of pine wilt disease. Full article

Background: Upper extremity deficits in unilateral cerebral palsy (UCP) severely restrict daily autonomy. Although movement-based priming is known to stimulate neuroplasticity, the distal transfer of lower extremity (LE) training to augment paretic upper limb (UL) function remains largely uninvestigated. This randomized controlled trial evaluated whether a 6-week LE cross-training (CT) priming regimen enhances UL functional restoration in pediatric UCP. Methods: Thirty-six children (6–8 years) were randomized to a conventional physical therapy cohort (n = 18) or an experimental CT cohort (n = 18). The CT group performed high-resistance contractions utilizing the non-paretic LE immediately preceding standard therapy. Blinded evaluations quantified Handgrip Strength (HGS) via dynamometry, grasping proficiency via the Peabody Developmental Motor Scales (PDMS-2), and gross dexterity via the Box and Block Test (BBT) pre and post intervention. Results: Analysis indicated a robust, near-significant between-group effect (Wilks’ Λ = 0.775, p = 0.057). While both cohorts achieved substantial internal improvements, the CT participants displayed superior developmental trajectories across all domains, notably in grasping age equivalence (34.28 ± 6.33 vs. 25.78 ± 3.26 months) and HGS (3.89 ± 0.79 vs. 3.03 ± 0.53 kg). Conclusions: LE cross-training priming may be a feasible adjunct, but it did not demonstrate statistically significant additional UL benefit versus standard rehabilitation in this sample. Therefore, these results should be interpreted as exploratory and hypothesis-generating. This potential cross-segmental transfer may theoretically operate via interhemispheric facilitation, warranting further investigation in larger, adequately powered trials. Full article

Salinity is a critical agricultural threat that reduces the productivity of several crops. Tomato (Solanum lycopersicum) is the world’s second most significant horticultural commodity, which struggles due to salt concentrations in irrigation water, even in hydroponic systems. This research evaluated seed priming treatments (hydro-, halo-, bacterio-, and halo-bacteriopriming) at different phenological stages under two salinity conditions (0 and 16 mM NaCl) to improve crop production. After evaluating physiological variables and multivariate statistical analyses, this study’s main breakthroughs are: Priming treatments modified the physiological, nutritional, and productive metabolism of tomato plants. Bacterio- and halo-bacteriopriming using an endophytic and halophytic bacterial consortium reduced germination time, enhancing uniformity and synchronizing seedling emergence. Bacteriopriming enhanced N, P, Ca and Zn absorption in seedlings. In the vegetative and reproductive stages, bacteriopriming consistently increased concentrations of K, Mg, and Zn in leaves and fruits but depleted Na uptake. Improving the nutritional balance resulted in not only a higher concentration of chlorophyll but also an increase in the yield and beta-carotene concentration in tomato fruits. The results demonstrated that halo-bacteriopriming may be a biotechnological strategy for mitigating saline stress, optimizing tomato growth and nutraceutical quality, because it outperformed the plant response in all stages of development compared to the control and hydro- and haloprimed treatments. Full article

This paper studies structural properties of semiprimes $N=pq$ in computational number theory, focusing on cases where the prime factors are close. We analyze the relationship between $\sqrt{N}$ and $\sqrt{\phi \left(N\right)}$ and show that, under a bounded prime gap condition, these quantities exhibit strong proximity. Specifically, assuming $|p-q|\le 2^{l/4}$ for an l-bit semiprime, we prove that the Euler totient function admits the exact representation $\phi \left(N\right)=N-1-2\lfloor \sqrt{N}\rfloor$. Based on this result, we develop an interval-based method for reconstructing $\phi \left(N\right)$ within a narrow neighborhood derived from square-root bounds, followed by a discriminant-based refinement step for recovering the prime factors. Experimental evaluation on large semiprimes, including RSA-type moduli of 4095 and 4096 bits, shows that the method operates efficiently under the stated structural condition using only elementary integer arithmetic. These results provide a theoretical characterization of semiprimes with small prime gaps and offer a framework for identifying structurally weak RSA moduli. This method, given its high efficiency when the prime factors are close to each other, can be regarded as an alternative to Fermat’s factorization method. In particular, for semiprime integers with a small prime gap (i.e., $|p-q|$ is small), the proposed approach exploits structural properties based on the proximity of square roots, thereby significantly accelerating the factorization process. Consequently, it not only aligns with the theoretical foundation of Fermat’s method but, under certain conditions, may also achieve comparable or even superior practical performance. Full article