Search Results (1,763)

Status epilepticus occurs when a seizure lasts more than five minutes or when multiple seizures occur with incomplete return to baseline. SE induces a myriad of pathological changes involving synaptic and extra-synaptic factors. The transition from a self-limiting seizure to a self-sustaining one is established by maladaptive receptor trafficking, whereby GABA_A receptors are progressively endocytosed while glutamatergic receptors (NMDA and AMPA) are transported to the synaptic membrane, causing excitotoxicity and alteration in glutamate-dependent downstream signaling. The subsequent influx of Ca²⁺ exposes neurons to increased levels of [Ca²⁺]i, which overwhelms mitochondrial buffering, resulting in irreversible mitochondrial membrane depolarization and mitochondrial injury. Oxidative stress resulting from mitochondrial leakage and increased production of reactive oxygen species activates the inflammasome and induces a damage-associated molecular pattern. Neuroinflammation perpetuates oxidative stress and exacerbates mitochondrial injury, thereby jeopardizing mitochondrial energy supply in a state of accelerated ATP consumption. Additionally, Ca²⁺ overload can directly damage neurons by activating enzymes involved in the breakdown of proteins, phospholipids, and nucleic acids. The cumulative effect of these effector pathways is neuronal injury and neuronal death. Surviving neurons undergo long-term alterations that serve as a substrate for epileptogenesis. This review highlights the multifaceted mechanisms underlying SE self-sustainability, pharmacoresistance, and subsequent epileptogenesis. Full article

Turbidity currents pose significant threats to offshore seabed infrastructures, including subsea hydrocarbon production facilities and submarine communication cables. These powerful underwater flows can damage pipelines, potentially causing hydrocarbon spills that endanger local communities, the environment, and negatively impact energy production infrastructures. Therefore, a comprehensive understanding of the spatio-temporal development and destructive force of turbidity currents is essential. While numerical computation of 3D flow, sediment transport, and substrate exchange is possible, field-scale simulations are computationally intensive. In this study, we develop a simplified morphodynamic approach to model the flow properties of channelized turbidity currents and the associated trends of sediment accretion and erosion. This model is applied to the Baco–Malaylay submarine system to investigate the dynamics of a significant turbidity current event that impacted a submarine pipeline offshore the Philippines. The modeling results align with available seabed assessments and observed erosion trends of the protective rock berm. Our simplified modeling approach shows good agreement with simulations from a fully 3D numerical model, demonstrating its effectiveness in providing valuable insights while reducing computational demands. Full article

In the present study, we evaluated the potential use of a humic substance (HS)-based biostimulant in mitigating drought stress in lettuce (Lactuca sativa L.) by comparing both root and foliar modes of application. To achieve this, lettuce plants were grown in a growth chamber on a solid substrate composed of vermiculite and perlite (3:1). Plants were exposed to drought conditions (50% of Field Capacity, FC) and 50% FC + HS applied as radicular (‘R’) and foliar (‘F’) at concentrations: R-HS 0.40 and 0.60 mL/L, respectively, and 7.50 and 10.00 mL/L, respectively, along with a control (100% FC). HSs were applied three times at 10-day intervals. Plant growth, nutrient concentration, lipid peroxidation, reactive oxygen species (ROS), and enzymatic and non-enzymatic antioxidants were estimated. Various photosynthetic and chlorophyll fluorescence parameters were also analyzed. The results showed that HS applications alleviated drought stress, increased plant growth, and reduced lipid peroxidation and ROS accumulation. HSs also improved the net photosynthetic rate, carboxylation efficiency, electron transport flux, and water use efficiency. Although foliar HSs showed a greater tendency to enhance shoot growth and photosynthetic capacity, the differences between the application methods were not significant. Hence, in this preliminary work, the HS-based product evaluated in this study demonstrated potential for alleviating drought stress in lettuce plants at the applied doses, regardless of the mode of application. This study highlights HS-based biostimulants as an effective and sustainable tool to improve crop resilience and support sustainable agriculture under climate change. However, further studies under controlled growth chamber conditions are needed to confirm these results before field trials. Full article

Membrane transporters play a crucial role in any cell. Identifying the substrates they translocate across membranes is important for many fields of research, such as metabolomics, pharmacology, and biotechnology. In this study, we leverage recent advances in deep learning, such as amino acid sequence embeddings with protein language models (pLMs), highly accurate 3D structure predictions with AlphaFold 2, and structure-encoding 3Di sequences from FoldSeek, for predicting substrates of membrane transporters. We test new deep learning features derived from both sequence and structure, and compare them to the previously best-performing protein encodings, which were made up of amino acid k-mer frequencies and evolutionary information from PSSMs. Furthermore, we compare the performance of these features either using a previously developed SVM model, or with a regularized feedforward neural network (FNN). When evaluating these models on sugar and amino acid carriers in A. thaliana, as well as on three types of ion channels in human, we found that both the DL-based features and the FNN model led to a better and more consistent classification performance compared to previous methods. Direct encodings of 3D structures with Foldseek, as well as structural embeddings with ProstT5, matched the performance of state-of-the-art amino acid sequence embeddings calculated with the ProtT5-XL model when used as input for the FNN classifier. Full article

In marine engineering applications, substituting conventional crushed stone coarse aggregates with coral aggregates offers dual advantages: reduced terrestrial quarrying operations and minimized construction material transportation costs. However, the inherent characteristics of coral aggregates—low bulk density, high porosity, and elevated water absorption capacity—adversely influence concrete workability and mechanical performance. To address these limitations, this investigation employed microbial-induced carbonate precipitation (MICP) for aggregate modification. The experimental design systematically evaluated the impacts of substrate concentration (1 mol/L) and mineralization period (14 days) on three critical parameters, mass gain percentage, water absorption reduction, and apparent density enhancement, across distinct particle size fractions (4.75–9.5 mm, 9.5–20 mm) and density classifications. Subsequent application trials assessed the performance of MICP-treated aggregates in marine concrete formulations. Results indicated that under a substrate concentration of 1 mol/L and mineralization period of 14 days, lightweight coral aggregates and coral aggregates within the 4.75–9.5 mm size fraction exhibited favorable modification effects. Specifically, their mass gain rates reached 11.75% and 11.22%, respectively, while their water absorption rates decreased by 32.22% and 34.75%, respectively. Apparent density increased from initial values of 1764 kg/m³ and 1930 kg/m³ to 2050 kg/m³ and 2207 kg/m³. Concrete mixtures incorporating modified aggregates exhibited enhanced workability and strength improvement at all curing ages. The 28-day compressive strengths reached 62.1 MPa (11.69% increment), 46.2 MPa (6.94% increment), and 60.1 MPa (14.91% increment) for the 4.75–9.5 mm, 9.5–20 mm, and continuous grading groups, respectively, compared to untreated counterparts. Full article

Efflux is one of the key mechanisms used by Gram-negative bacteria to reduce internal antibiotic concentrations. These active transport systems recognize and expel a wide range of toxic molecules, including antibiotics, thereby contributing to reduced antibiotic susceptibility and allowing the bacteria to acquire additional resistance mechanisms. To date, unlike other resistance mechanisms such as enzymatic modification or target mutations/masking, efflux is challenging to detect and counteract in clinical settings, and no standardized methods are currently available to diagnose or inhibit this mechanism effectively. This review first outlines the structural and functional features of major efflux pumps in Gram-negative bacteria and their role in antibiotic resistance. It then explores various strategies used to curb their activity, with a particular focus on efflux pump inhibitors under development, detailing their structural classes, modes of action, and pharmacological potential. We discuss the main obstacles to their development, including the structural complexity and substrate promiscuity of efflux mechanisms, the limitations of current screening methods, pharmacokinetic and tissue distribution issues, and the risk of off-target toxicity. Overcoming these multifactorial barriers is essential to the rational development of less efflux-prone antibiotics or of efflux pump inhibitors. Full article

The kinetics of liquid transport in textiles are determined by the thermodynamic boundary conditions and the substrate’s structure. The knitting process offers a wide range of possibilities for modifying the fabric structure, making it ideal for high-performance garments and technical applications. Given the highly complex nature of textiles’ interaction with liquids, this paper investigates how fabric structure affects combined wicking and drying behaviour. This facilitates comprehension of the underlying transport processes on the yarn and fabric scale, which is important for understanding the behaviour of the material as a whole. The presented experiment combines analysis of wicking through radial liquid spread using imaging techniques and analysis of the drying process through gravimetric measurement of evaporation. Eight samples of single jersey knitted fabrics were produced using polyester yarns of different texturization and fibre diameters on flat and circular knitting machines. The fabrics demonstrate significantly different wicking behaviours depending on their structure. The fabric’s drying time and rate are directly linked to the macroscopic spread of the liquid. Large inter-yarn pores hinder liquid spread. For the lowest liquid saturations, the yarn structure plays a critical role. Using fine, dense yarns can hinder convective drying within the yarn. Textured yarns tend to exhibit higher specific drying rates. The results offer a comprehensive insight into the interplay between the fabric’s structure and its wicking and drying behaviour, which is crucial for the development of functional fabrics in the knitting process. Full article

Firstly, this paper reviews the fundamental theories of solid surface wettability and contact angle hysteresis. Subsequently, it further introduces four typical wettability-engineered surfaces with low hysteresis (superhydrophobic, superamphiphobic, super-slippery, and liquid-like smooth surfaces). Finally, it focuses on the latest research progress in the field of droplet manipulation on open planar surfaces with engineered wettability. To achieve droplet manipulation, the core driving forces primarily stem from natural forces guided by bioinspired gradient surfaces or the regulatory effects of external fields. In terms of bioinspired self-propelled droplet movement, this paper summarizes research inspired by natural organisms such as desert beetles, cacti, self-aligning floating seeds of emergent plants, or water-walking insects, which construct bioinspired special gradient surfaces to induce Laplace pressure differences or wettability gradients on both sides of droplets for droplet manipulation. Moreover, this paper further analyzes the mechanisms, advantages, and limitations of these self-propelled approaches, while summarizing the corresponding driving force sources and their theoretical formulas. For droplet manipulation under external fields, this paper elaborates on various external stimuli including electric fields, thermal fields, optical fields, acoustic fields, and magnetic fields. Among them, electric fields involve actuation mechanisms such as directly applied electrostatic forces and indirectly applied electrocapillary forces; thermal fields influence droplet motion through thermoresponsive wettability gradients and thermocapillary effects; optical fields cover multiple wavelengths including near-infrared, ultraviolet, and visible light; acoustic fields utilize horizontal and vertical acoustic radiation pressure or acoustic wave-induced acoustic streaming for droplet manipulation; the magnetic force acting on droplets may originate from their interior, surface, or external substrates. Based on these different transport principles, this paper comparatively analyzes the unique characteristics of droplet manipulation under the five external fields. Finally, this paper summarizes the current challenges and issues in the research of droplet manipulation on the open planar surfaces and provides an outlook on future development directions in this field. Full article

Quercetin is a biologically active flavonoid compound that exerts numerous beneficial effects in humans and animals, including anti-diabetic activity. Its action has been explored in rodent models of type 1 and type 2 diabetes. It was revealed that quercetin mitigated diabetes-related hormonal and metabolic disorders and reduced oxidative and inflammatory stress. Its anti-diabetic effects were associated with advantageous changes in the relevant enzymes and signaling molecules. Quercetin positively affected, among others, superoxide dismutase, catalase, glutathione peroxidase, glucose transporter-2, glucokinase, glucose-6-phosphatase, glycogen phosphorylase, glycogen synthase, glycogen synthase kinase-3β, phosphoenolpyruvate carboxykinase, silent information regulator-1, sterol regulatory element-binding protein-1, insulin receptor substrate 1, phosphoinositide 3-kinase, and protein kinase B. The available data support the conclusion that the action of quercetin was pleiotropic since it alleviates a wide range of diabetes-related disorders. Moreover, no side effects were observed during treatment with quercetin in rodents. Given that human diabetes affects a large part of the population worldwide, the results of animal studies encourage clinical trials to evaluate the potential of quercetin as an adjunct to pharmacological therapies. Full article

This review surveys recent advances and emerging prospects in phase-transfer catalysis (PTC) for fuel desulfurization. In response to increasingly stringent environmental regulations, the removal of sulfur from transportation fuels has become imperative for curbing SO_x emissions. Conventional hydrodesulfurization (HDS) operates under severe temperature–pressure conditions and displays limited efficacy toward sterically hindered thiophenic compounds, motivating the exploration of non-hydrogen routes such as oxidative desulfurization (ODS). Within ODS, PTC offers distinctive benefits by shuttling reactants across immiscible phases, thereby enhancing reaction rates and selectivity. In particular, PTC enables efficient migration of organosulfur substrates from the hydrocarbon matrix into an aqueous phase where they are oxidized and subsequently extracted. The review first summarizes the deployment of classic PTC systems—quaternary ammonium salts, crown ethers, and related agents—in ODS operations and then delineates the underlying phase-transfer mechanisms, encompassing reaction-controlled, thermally triggered, photo-responsive, and pH-sensitive cycles. Attention is next directed to a new generation of catalysts, including quaternary-ammonium polyoxometalates, imidazolium-substituted polyoxometalates, and ionic-liquid-based hybrids. Their tailored architectures, catalytic performance, and mechanistic attributes are analyzed comprehensively. By incorporating multifunctional supports or rational structural modifications, these systems deliver superior desulfurization efficiency, product selectivity, and recyclability. Despite such progress, commercial deployment is hindered by the following outstanding issues: long-term catalyst durability, continuous-flow reactor design, and full life-cycle cost optimization. Future research should, therefore, focus on elucidating structure–performance relationships, translating batch protocols into robust continuous processes, and performing rigorous environmental and techno-economic assessments to accelerate the industrial adoption of PTC-enabled desulfurization. Full article

Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities. Objectives/Methods: This study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review. Results: Enzyme activity, molecular data, and phenotypic assessments are described to explore genotype–phenotype correlations and identify diagnostic challenges. Conclusions: These findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members. Full article

This study systematically investigated the corrosion evolution and protective mechanisms of X80 pipeline steel in Xinjiang’s saline soil environments under freeze–thaw cycling conditions. Combining regional soil characterization with laboratory-constructed corrosion systems, we employed electrochemical impedance spectroscopy, potentiodynamic polarization, and surface analytical techniques to quantify temporal–spatial corrosion behavior across 30 freeze–thaw cycles. Experimental results revealed a distinctive corrosion resistance pattern: initial improvement (cycles 1–10) attributed to protective oxide layer formation, followed by accelerated degradation (cycles 10–30) due to microcrack propagation and chloride accumulation. Synchrotron X-ray diffraction analyses identified sulfate–chloride ion synergism as the primary driver of localized corrosion disparities in heterogeneous soil matrices. A comparative evaluation of asphalt-coated specimens demonstrated a 62%–89% corrosion rate reduction, with effectiveness directly correlating with coating integrity and thickness (200–500 μm range). Molecular dynamics simulations using Materials Studio revealed atomic-scale ion transport dynamics at coating–substrate interfaces, showing preferential Cl⁻ permeation through coating defects. These multiscale findings establish quantitative relationships between environmental stressors, coating parameters, and corrosion kinetics, providing a mechanistic framework for optimizing protective coatings in cold-region pipeline applications. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Cold environments challenge the structural and functional integrity of membrane proteins, requiring specialized adaptations to maintain activity under low thermal energy. Here, we investigate the molecular basis of cold tolerance in the peptide transporter PepT1 from the Antarctic icefish (Chionodraco hamatus, ChPepT1) using molecular dynamics simulations, binding free energy calculations (MM/GBSA), and dynamic network analysis. We compare ChPepT1 to its human ortholog (hPepT1), a non-cold-adapted variant, to reveal key features enabling psychrophilic function. Our simulations show that ChPepT1 displays enhanced global flexibility, particularly in domains adjacent to the substrate-binding site and the C-terminal domain (CTD). While hPepT1 loses substrate binding affinity as temperature increases, ChPepT1 maintains stable peptide interactions across a broad thermal range. This thermodynamic buffering results from temperature-sensitive rearrangement of hydrogen bond networks and more dynamic lipid interactions. Importantly, we identify a temperature-responsive segment (TRS, residues 660–670) within the proximal CTD that undergoes an α-helix to coil transition, modulating long-range coupling with transmembrane helices. Dynamic cross-correlation analyses further suggest that ChPepT1, unlike hPepT1, reorganizes its interdomain communication in response to temperature shifts. Our findings suggest that cold tolerance in ChPepT1 arises from a combination of structural flexibility, resilient substrate binding, and temperature-sensitive interdomain dynamics. These results provide new mechanistic insight into thermal adaptation in membrane transporters and offer a framework for engineering proteins with enhanced functionality in extreme environments. Full article

Epitaxial growth of β-Ga₂O₃ nanowires on silicon substrates was realized by the low-pressure chemical vapor deposition (LPCVD) method. The as-grown Si/Ga₂O₃ heterojunctions were employed in the Underwater DUV detection. It is found that the carrier type as well as the carrier concentration of the silicon substrate significantly affect the performance of the Si/Ga₂O₃ heterojunction. The p-Si/β-Ga₂O₃ (2.68 × 10¹⁵ cm⁻³) devices exhibit a responsivity of up to 205.1 mA/W, which is twice the performance of the devices on the n-type substrate (responsivity of 93.69 mA/W). Moreover, the devices’ performance is enhanced with the increase in the carrier concentration of the p-type silicon substrates; the corresponding device on the high carrier concentration substrate (6.48 × 10¹⁷ cm⁻³) achieves a superior responsivity of 845.3 mA/W. The performance enhancement is mainly attributed to the built-in electric field at the p-Si/n-Ga₂O₃ heterojunction and the reduction in the Schottky barrier under high carrier concentration. These findings would provide a strategy for optimizing carrier transport and interface engineering in solar-blind UV photodetectors, advancing the practical use of high-performance solar-blind photodetectors for underwater application. Full article