Search Results (947)

The functional role of MAPKK genes in potato (Solanum tuberosum L.) under high-temperature stress remains unexplored, despite their critical importance in stress signaling and yield protection. We characterized StMAPKK1, a novel group D MAPKK localized to plasma membrane/cytoplasm. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed cultivar-specific upregulation in potato (‘Atlantic’ and ‘Desiree’) leaves under heat stress (25 °C, 30 °C, and 35 °C). Transgenic lines overexpressing (OE) StMAPKK1 exhibited elevated antioxidant enzyme activity, including ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD), mitigating oxidative damage. Increased proline and chlorophyll accumulation and reduced oxidative stress markers, hydrogen peroxide (H₂O₂) and malondialdehyde (MDA), indicate improved cellular redox homeostasis. The upregulation of key antioxidant and heat stress-responsive genes (StAPX, StCAT1/2, StPOD12/47, StFeSOD2/3, StMnSOD, StCuZnSOD1/2, StHSFA3 and StHSP20/70/90) strengthened the enzymatic defense system, enhanced thermotolerance, and improved photosynthetic efficiency, with significant improvements in net photosynthetic rate (Pn), transpiration rate (E), and stomatal conductance (Gs) under heat stress (35 °C) in StMAPKK1-OE plants. Superior growth and biomass (plant height, plant and its root fresh and dry weights, and tuber yield) accumulation, confirming the positive role of StMAPKK1 in thermotolerance. Conversely, RNA interference (RNAi)-mediated suppression of StMAPKK1 led to a reduction in enzymatic activity, proline content, and chlorophyll levels, exacerbating oxidative stress. Downregulation of antioxidant-related genes impaired ROS scavenging capacity and declines in photosynthetic efficiency, growth, and biomass, accompanied by elevated H₂O₂ and MDA accumulation, highlighting the essential role of StMAPKK1 in heat stress adaptation. These findings highlight StMAPKK1’s potential as a key genetic target for breeding heat-tolerant potato varieties, offering a foundation for improving crop resilience in warming climates. Full article

Background: 1,2,3,4,5-pentathiepines (PTEs) are compounds originally identified in marine ascidians and are currently under investigation for their promising pharmacological properties, particularly as potential antineoplastic agents. Objectives: In this study, we investigated the antineoplastic properties of a series of ten indolizine-based PTEs, comprising eight previously reported compounds and two newly synthesized derivatives. Methods: These compounds were evaluated against a panel of human cancer cell lines of diverse tissue origins, as well as, for the first time, on non-cancerous CR9 fibroblasts to assess their cytotoxic selectivity. In addition, their effects were tested on 3D spheroid models, providing preliminary insights into their potential in vivo efficacy. Initial screening focused on cell viability, followed by a more detailed characterization of the most active compounds in terms of their ability to induce apoptosis, necrosis, cell cycle arrest, and reactive oxygen species (ROS) generation. The anti-migratory activity of PTEs and a newly adapted assay to confirm sulfur species release in the cells were also performed for the first time. Results and Conclusions: Our findings reveal that four PTEs bearing hydrophilic, hydrogen-bonding functional groups, particularly the two inspired by natural analogs, exhibited the most potent anticancer activity. Full article

Neuro-oncology focuses on the diagnosis and treatment of brain tumors, which, despite their rarity, are associated with high mortality due to their invasiveness and limited treatment options. Emerging evidence suggests that dopamine (DA), a neurotransmitter crucial for cognitive and emotional processes, and its receptors may influence tumor growth and the tumor microenvironment. This study aimed to evaluate the potential anticancer effects of repurposed antipsychotic dopamine-targeting drugs (Clozapine, CLZ; Pimozide, PIM; Olanzapine, OLZ; and Risperidone, RIS) and antiemetic drugs (Domperidone, DOM; Droperidol, DRO) on neuroblastoma (SH-SY5Y) and glioblastoma (A172) cell lines, and to assess whether their efficacy is modulated by oxidative stress and DA synthesis. The drugs were first tested individually, followed by co-treatment with tyrosine (Tyr), a dopamine precursor, and hydrogen peroxide (H₂O₂), an inducer of oxidative stress. Additionally, drug activity was evaluated in the simultaneous presence of H₂O₂ and Tyr. CLZ exhibited the highest cytotoxicity in both cell lines, suggesting strong anticancer potential and also synergism among the different combinations, particularly in SH-SY5Y. Liquid chromatography of the extracellular medium showed greater Tyr consumption in SH-SY5Y compared to A172 cells, indicating a higher dependence on extracellular Tyr to mitigate drug- and/or stress-induced cytotoxicity. In summary, several of the repurposed antipsychotics demonstrated cytotoxic effects on central nervous system tumor cells, with CLZ showing the most promising activity, even under oxidative stress conditions. These findings support further investigation into dopamine-targeting drugs as potential therapeutic agents in neuro-oncology. Full article

The point-kernel (PK) technique has a long history in applied radiation shielding, originating from the early days of digital computers. The PK technique applied to gamma-ray attenuation is one of many successful applications, based on the linear superposition principle applied to distributed radiation sources. Mathematically speaking, the distributed source will produce a detector response equivalent to the numerical integration of the radiation received from an equivalent number of point sources. In this treatment, there is no interference between individual point sources, while inherent limitations of the PK method are its inability to simulate gamma scattering in shields and the usage of simple boundary conditions. The PK method generally works for gamma-ray shielding with corrective B-factor for scattering and only specifically for fast neutron attenuation in a hydrogenous medium with the definition of cross section removal. This paper presents theoretical and programming aspects of the PK program developed for a distributed source of photons (line, disc, plane, sphere, slab volume, etc.) and slab shields. The derived flux solutions go beyond classical textbooks as they include the analytical integration of Taylor B-factor, obtaining a closed form readily suitable for programming. The specific computational modules are unified with a graphical user interface (GUI), assisting users with input/output data and visualization, developed for the fast radiological characterization of simple shielding problems. Numerical results of the selected PK test cases are presented and verified with the CADIS hybrid shielding methodology of the MAVRIC/SCALE6.1.3 code package from the ORNL. Full article

This scoping review investigates the digital transition of critical energy infrastructure (CEI) in maritime ports, which are increasingly vital as energy hubs amid global decarbonisation efforts. Recognising the growing role of ports in integrating offshore renewables, hydrogen, and LNG systems, the study examines how digital technologies (such as automation, IoT, and AI) support the resilience, efficiency, and sustainability of port-based CEI. A multifaceted search strategy was implemented to identify relevant academic and grey literature. The search was performed between January 2025 and 30 April 2025. The strategy focused on databases such as Scopus. Due to limitations encountered in retrieving sufficient, directly relevant academic papers from databases alone, the search strategy was systematically expanded to include grey literature such as reports, policy documents, and technical papers from authoritative industry, governmental, and international organisations. Employing Arksey and O’Malley’s framework and PRISMA-ScR (scoping review) guidelines, the review synthesises insights from 62 academic and grey literature sources to address five core research questions relating to the current state, challenges, importance, and future directions of digital CEI in ports. Literature distribution of articles varies across continents, with Europe contributing the highest number of publications (53%), Asia (24%) and North America (11%), while Africa and Oceania account for only 3% of the publications. Findings reveal significant regional disparities in digital maturity, fragmented governance structures, and underutilisation of digital systems. While smart port technologies offer operational gains and support predictive maintenance, their effectiveness is constrained by siloed strategies, resistance to collaboration, and skill gaps. The study highlights a need for holistic digital transformation frameworks, cross-border cooperation, and tailored approaches to address these challenges. The review provides a foundation for future empirical work and policy development aimed at securing and optimising maritime port energy infrastructure in line with global sustainability targets. Full article

Four new minor monosulfated triterpene penta- and hexaosides, cladolosides S (1), S₁ (2), T (3), and T₁ (4), were isolated from the Vietnamese sea cucumber Cladolabes schmeltzii (Sclerodactylidae, Dendrochirotida). The structures of the compounds were established based on extensive analysis of 1D and 2D NMR spectra as well as HR-ESI-MS data. Cladodosides S (1), S₁ (2) and T (3), T₁ (4) are two pairs of dehydrogenated/hydrogenated compounds that share identical carbohydrate chains. The oligosaccharide chain of cladolosides of the group S is new for the sea cucumber glycosides due to the presence of xylose residue attached to C-4 Xyl1 in combination with a sulfate group at C-6 MeGlc4. The oligosaccharide moiety of cladolosides of the group T is unique because of the position of the sulfate group at C-3 of the terminal sugar residue instead of the 3-O-Me group. This suggests that the enzymatic processes of sulfation and O-methylation that occur during the biosynthesis of glycosides can compete with each other. This can presumably occur due to the high level of expression or activity of the enzymes that biosynthesize glycosides. The mosaicism of glycoside biosynthesis (time shifting or dropping out of some biosynthetic stages) may indicate a lack of compartmentalization inside the cells of organism producers, leading to a certain degree of randomness in enzymatic reactions; however, this also offers the advantage of providing chemical diversity of the glycosides. Analysis of the hemolytic activity of a series of 26 glycosides from C. schmeltzii revealed some patterns of structure–activity relationships: the presence or absence of 3-O-methyl groups has no significant impact, hexaosides, which are the final products of biosynthesis and predominant compounds of the glycosidic fraction of C. schmeltzii, are more active than their precursors, pentaosides, and the minor tetraosides, cladolosides of the group A, are weak membranolytics and therefore are not synthesized in large quantities. Two glycosides from C. schmeltzii, cladolosides D (18) and H₁ (26), display selectivity of cytotoxic action toward triple-negative breast cancer cells MDA-MB-231, while remaining non-toxic in relation to normal mammary cells MCF-10A. Quantitative structure–activity relationships (QSAR) were calculated based on the correlational analysis of the physicochemical properties and structural features of the glycosides and their hemolytic and cytotoxic activities against healthy MCF-10A cells and cancer MCF-7 and MDA-MB-231 cell lines. QSAR highlighted the complexity of the relationships as the cumulative effect of many minor contributions from individual descriptors can have a significant impact. Furthermore, many structural elements were found to have different effects on the activity of the glycosides against different cell lines. The opposing effects were especially pronounced in relation to hormone-dependent breast cancer cells MCF-7 and triple-negative MDA-MB-231 cells. Full article

Hydrogen is a potential source of imminent clean energy in the future, with its transportation playing a crucial role in allowing large-scale deployment. The challenge lies in selecting an effective, sustainable, and scalable transportation alternative. This study develops a multi-criteria decision-making (MCDM) framework based on the intuitionistic fuzzy analytic hierarchy process (IF-AHP) to evaluate land-based hydrogen transportation alternatives across Canada. The framework includes uncertainty and decision-maker hesitation through the application of triangular intuitionistic fuzzy numbers (TIFNs). Seven factors, their subsequent thirty-three subfactors, and three alternatives to hydrogen transportation were identified through a literature review. Pairwise comparison was aggregated among factors, subfactors, and alternatives from three decision makers using an intuitionistic fuzzy weighted average, and priority weights were computed using entropy-based weight. The results show that safety and economic efficiency emerged as the most influential factors in the evaluation of hydrogen transportation alternatives, followed by environmental impact, security, and social impact and public health in ascending order. Among the alternatives, tube truck transport obtained the highest overall weight (0.3551), followed by pipelines (0.3272) and rail lines (0.3251). The findings suggest that the tube ruck is currently the most feasible transport option for land-based hydrogen distribution that aims to provide a transition of Canada’s energy mix. Full article

Abiotic stress poses a serious challenge in agriculture. Salinity inhibits crop growth and yields by disrupting ionic homeostasis and osmotic balance. One critical mechanism of salt tolerance is the activation of the Salt Overly Sensitive (SOS) signaling pathway. Investigating this pathway in halophytic plants offers valuable insights into the molecular mechanisms underlying salt stress tolerance. This study explores the structure and function of SOS3/CBL4 from the gray mangrove, Avicennia marina (AmSOS3). Sequence analysis revealed that AmSOS3 shares significant similarities with orthologs of SOS3/CBL4, including Arabidopsis thaliana (AtSOS3). All essential functional domains of SOS3, including the four EF-hands, as well as the N-myristoylation and S-acylation motif, were conserved in AmSOS3. Structural modeling, using Modeller, predicted that AmSOS3 forms a homodimer stabilized by a hydrogen bond at the serine 140 position. Functional characterization further demonstrated that AmSOS3 complements the sos3-1 mutation in A. thaliana, thus confirming that AmSOS3 is an ortholog of AtSOS3. Overexpression of AmSOS3 in wild-type A. thaliana enhanced tolerance under salinity stress. The transgenic lines displayed reduced reactive oxygen species (ROS) accumulation and increased ROS-scavenging enzyme activity. These findings indicate that AmSOS3 plays a critical role in improving salt stress tolerance and maintaining cellular homeostasis. Full article

Hydrogen-powered aircraft constitute a transformative innovation in aviation, motivated by the imperative for sustainable and environmentally friendly transportation solutions. This paper aims to concentrate on the design of hydrogen powertrains employing a system approach to propose representative design models for distribution and propulsion systems. Initially, the requirements for powertrain design are formalized, and a use-case-driven analysis is conducted to determine the functional and physical architectures. Subsequently, for each component pertinent to preliminary design, an analytical model is proposed for multidisciplinary analysis and optimization for powertrain sizing. A double-wall pipe model, incorporating foam and vacuum multi-layer insulation, was developed. The internal and outer pipes sizing were performed in accordance with standards for hydrogen piping design. Valves sizing is also considered in the present study, following current standards and using data available in the literature. Furthermore, models for booster pumps to compensate pressure drop and high-pressure pumps to elevate pressure at the combustion chamber entrance are proposed. Heat exchanger and evaporator models are also included and connected to a burning hydrogen engine in the sizing process. An optimal liner pipe diameter was identified, which minimizes distribution systems weight. We also expect a reduction in engine length and weight while maintaining equivalent thrust. Full article

Peanut (Arachis hypogaea L.), a vital oilseed and cash crop, faces yield limitations due to abiotic stresses. The 9-cis-epoxycarotenoid dioxygenase (NCED) enzyme, a key enzyme in abscisic acid (ABA) biosynthesis regulating plant development and stress responses, remains mechanistically uncharacterized in peanut abiotic stress tolerance. In this study, we isolated a novel gene, AhNCED4, from the salt-tolerant mutant M24. The expression of AhNCED4 was strongly induced by NaCl, PEG6000, and ABA in peanut huayu20. Overexpression of AhNCED4 enhanced salt and drought tolerance in Arabidopsis. Transgenic overexpression of AhNCED4 improved salt and stress resistance through upregulated ROS-scavenging genes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) with elevated enzymatic activities while reducing malondialdehyde (MDA), superoxide anion (O²⁻), and hydrogen peroxide (H₂O₂) accumulation compared to wild-type plants. Further research showed that the chlorophyll fluorescence parameters of transgenic lines were significantly increased, while light damage was significantly reduced. These findings establish AhNCED4 as a critical regulator of stress adaptation and an excellent candidate gene for resistance breeding in peanut. Full article

Oxidative stress poses a significant challenge in livestock production, impairing intestinal function, nutrient absorption, and overall animal performance. Uncoupling protein 2 (UCP2) is a mitochondrial regulator known for its protective effects against oxidative damage, but its specific function in porcine intestinal epithelial cells and its regulation by genipin—a natural UCP2 inhibitor with potential therapeutic properties—remains unclear. In this study, we cloned and overexpressed the porcine UCP2 gene in intestinal porcine epithelial cells (IPEC-J2), generating a stable UCP2-overexpressing cell line (IPEC-J2-UCP2). Under hydrogen peroxide-induced oxidative stress, UCP2 overexpression significantly improved cell viability, reduced reactive oxygen species (ROS) levels, and enhanced antioxidant enzyme activities (SOD, GPx, and CAT). Additionally, UCP2 upregulated the anti-apoptotic gene Bcl-2 and downregulated pro-apoptotic genes (Fas, Caspase-3, and Bax), indicating a protective role against oxidative stress-induced apoptosis. We also investigated the regulatory effects of genipin on UCP2. Under non-stress conditions, genipin mildly promoted anti-apoptotic gene expression. However, under oxidative stress, genipin strongly inhibited UCP2 expression, exacerbated ROS accumulation, reduced cell viability, and increased expression of pro-apoptotic markers, particularly Caspase-3 and Bax. These findings reveal that UCP2 plays a critical role in protecting porcine intestinal epithelial cells from oxidative injury and that genipin exerts context-dependent effects on cell fate by modulating UCP2. This study provides a mechanistic basis for targeting UCP2 to manage oxidative stress and improve intestinal health and performance in pigs. Full article

Formononetin is widely used in anti-tumor research, but its poor water solubility leads to low absorption and poor utilization efficiency in vivo, limiting further development. The triphenylphosphine cation was partially attached to the 7-position hydroxyl group of formononetin to specifically target it into the mitochondria of tumor cells to enhance the anti-tumor effect. Detailed structural characterization via ¹H-NMR and ¹³C-NMR analysis confirmed the physical properties and chemical structures of 21 newly synthesized derivatives. The effects of these derivatives on tumor cells were assessed by in vitro and computational methods. MTT results from four tumor cell lines showed that formononetin derivatives containing triphenylphosphine had stronger anti-tumor activity than formononetin and exhibited more cytotoxic effects in cancer cells than in normal cells. In particular, the final product 2c (IC₅₀ = 12.19 ± 1.52 μM) showed more potent anti-tumor activity against A549 cells. It was also superior to formononetin and 5-FU. To identify the potential biological targets, the core-expressed gene SHMT2 in lung cancer mitochondria was screened using network pharmacology technology, and molecular docking analysis confirmed the stable binding of the end products to the amino acid residues of the core genes through the formation of hydrogen bonds and via other interactions. In addition, molecular docking simulations further confirmed that the end product exhibited excellent stability when bound to SHMT2. These results suggest that triphenylphosphine-containing formononetin derivatives are worthy of further exploration in the search for novel drug candidates for the treatment of cancer. Full article

Background/Objectives: In vitro, vancomycin (VAN) and tetrahydrolipstatin (THL) together have been shown to synergistically inhibit Mycobacterium tuberculosis (Mtb), the world’s most infectious killer. The poor oral bioavailability of VAN and THL and predominant tropism of Mtb infection to the lungs and alveolar macrophages make pulmonary administration highly attractive. This study aimed to develop and assess the efficacy of dry powders for inhalation of VAN microparticles embedded with THL. Methods: The dry powders produced by spray-drying, with or without hydrogenated castor oil (HCO), were characterized for their physicochemical properties among others by HPLC-DAD. The fast-screening impactor was used to determine powder aerodynamic properties, and VAN and THL releases were established from the paddle over disk method. Biological activities were assessed in a new M. bovis-infected macrophage model and in Mtb-infected mice. Results and Discussion: The addition of 25% HCO enables co-deposition (fine particle dose) at the desired weight ratio and co-releasing of VAN and THL in aqueous media. Microparticles with 0% to 50% HCO drastically reduced cytoplasmic Mycobacterium bovis survival (99.9% to 62.5%, respectively), with higher efficacy at low HCO concentration. Consequently, VAN/THL with or without 25% HCO was evaluated in Mtb-infected mice. Although no decrease in Mtb lung burden was observed after two weeks of administration, the endotracheal administration of VAN 500 mg/kg and THL 50 mg/kg with 25% HCO administrated three times during five days concomitantly with daily oral rifampicin (10 mg/kg) demonstrated 2-fold bacterial burden reduction compared to the group treated with RIF alone. Conclusions: HCO was crucial for obtaining a fine particle dose at the synergistic weight ratio (VAN/THL 10:1) and for releasing both drugs in aqueous media. With oral administration of the first-line rifampicin, the dry powder VAN/THL/25% HCO was able to exert a potential anti-tubercular effect in vivo in Mtb-infected mice after five days. Full article

This study investigates the effects of different sealing materials, steel lining and Fiber-Reinforced Polymer (FRP), on the thermodynamic properties of hydrogen storage in lining rock caverns (LRCs). A thermodynamic coupling equation for hydrogen storage in LRCs was developed, and its validity was confirmed by comparison with simulations and data from the Huntorf power station. The leakage rate, temperature changes, and stress distribution of steel and FRP sealing layers with varying thicknesses were analyzed over a 30-day period. The results show that the leakage rate of the FRP layer decreases significantly with thickness, with a peak leakage of 1.3 g/s for the 10 mm layer, stabilizing at around 0.1 g/s for the 100 mm layer. Temperature fluctuations within the cavern are periodic, with more pronounced changes in the FRP layer as its thickness increases. Steel lining experiences minimal temperature changes. Additionally, increasing the FRP thickness results in larger fluctuations in the principal stress of both the sealing and lining layers, impacting the surrounding rock mass. The FRP lining experiences higher tensile stress, while the steel lining shows smaller changes. A thicker FRP layer also increases normal and shear stresses in the surrounding rock, potentially affecting cavern stability. These findings emphasize the importance of selecting appropriate sealing materials and thicknesses to improve the efficiency and stability of hydrogen storage systems. Full article

Mn(III)– and Co(III)–salen complexes (Mn-1 and Co-2) have been synthesized by a simple one-pot procedure through oxidation of Mn(II) and Co(II) precursors in air. X-ray structural analysis reveals that both complexes adopt similar coordination modes, including a typical square planar metal/salen coordination sphere, which is further occupied by two axial ligands, i.e., an acetate anion and a water molecule. Despite their structural similarity, they are not isomorphous given their distinct cell parameters. In the solid-state structures, both complexes exist as hydrogen-bonded dimers through hydrogen bonding interactions between the axially coordinating water molecules and outer O₄ cavity from another molecule of the complex. The reductive activity of both complexes has been explored. While the reaction of Mn-1 with potassium triethylborohydride was unsuccessful, leading to a complicated mixture, the use of Co-2 furnished the formation of a novel product (CoK-3) that was isolated as red crystals in reasonable yield. CoK-3 was characterized as a heterometallic dimer involving the coordination of a K⁺ ion within the O₄ cavity of a semi-hydrogenated salen/cobalt complex while the cobalt center has been reduced from Co(III) to Co(II). In addition, an attempt at reducing Co-2 with pinacolborane resulted in the isolation of crystals of Co-4, whose structure was determined as a simple square planar Co^II–salen complex. Finally, three complexes (Mn-1, Co-2 and CoK-3) have been investigated for their cytotoxic activities against two human breast cancer cell lines (MCF-7 and MDA-MB 468) and a normal breast epitheliel cell line (MCF-10A), with cisplatin used as a reference in order to discover potential drug candidates that may compete with cisplatin. The results reveal that Co-2 can be a promising drug candidate, specifically for the MCF-7 cancer cells, with minimal damage to healthy cells. Full article