Search Results (685)

Nitric oxide (NO) has a dual effect on mitochondria. Incubating liver mitochondria with NO improves oxidative phosphorylation (OXPHOS) efficiency by decreasing state 4 respiration more than ATP synthesis and preventing mitochondrial permeability transition pore (mPTP) opening. We evaluated the effect of L-arginine (L-arg), an NO donor, on isolated liver mitochondrial respiration and mPTP in sepsis. Male mice were subjected to cecal ligation and perforation (CLP) with saline resuscitation or sham. After 8, 24, and 48 h, with and without L-arg, we measured isolated liver mitochondrial respiration and cytochrome c oxidase (COX) activity using polarographic methods and calcium retention capacity (CRC) to assess the mPTP and NO metabolites via the Griess reaction. Mitochondrial NO synthase (mtNOS) was identified by Western blot. CLP decreased state 3 respiration at 24 and 48 h, decreased COX activity at 8, 24, and 48 h, and increased state 4 respiration and decreased the respiratory control ratio (RCR) and CRC at 48 h. L-arg increased NO levels at 8 h, decreased state 4 respiration more than state 3 respiration (−39% versus −12%) at 48 h, decreased the CRC in the CLP groups at 24 and 48 h, but did not improve RCR. Our data suggests that L-arg does not restore liver mitochondrial OXPHOS efficiency or prevent mPTP opening in the late or recovery phases of sepsis. Full article

The study of metabolic abnormalities regarding mitochondrial respiration and energy production has significantly advanced our understanding of cell biology and molecular mechanisms underlying cardiovascular diseases (CVDs). Mitochondria provide 90% of the energy required for maintaining normal cardiac function and are central to heart bioenergetics. During the initial phase of heart failure, mitochondrial number and function progressively decline, causing a decrease in oxidative metabolism and increased glucose uptake and glycolysis, leading to ATP depletion and bioenergetic starvation, finally contributing to overt heart failure. Compromised mitochondrial bioenergetics is associated with vascular damage in hypertension, vascular remodeling in pulmonary hypertension and acute cardiovascular events. Thus, mitochondrial dysfunction, leading to impaired ATP production, excessive ROS generation, the opening of mitochondrial permeability transition pores and the activation of apoptotic and necrotic pathways, is revealed as a typical feature of common CVDs. Molecules able to positively modulate cellular metabolism by improving mitochondrial bioenergetics and energy metabolism and inhibiting oxidative stress production are expected to exert beneficial protective effects in the heart and vasculature. This review discusses recent advances in cardiovascular research through the study of cellular bioenergetics in both chronic and acute CVDs. Emerging therapeutic strategies, specifically targeting metabolic modulators, mitochondrial function and quality control, are discussed. Full article

Ultra-tight gas reservoirs present severe flow constraints due to complex interactions between rock–fluid properties and hydraulic fracturing. This study investigates the impact of unconventional capillary pressure correlations and permeability jail effects on post-fracture cleanup in multiple-fractured horizontal wells (MFHWs) using high-resolution numerical simulations. A novel modelling approach is applied to represent both weak and strong permeability jail phenomena in heterogeneous rock systems. A comprehensive suite of parametric simulations evaluates gas production loss (GPL) and produced fracture fluid (PFF) across varying fracture fluid volumes, shut-in times, drawdown pressures, and matrix permeabilities. The analysis leverages statistically designed experiments and response surface models to isolate the influence of rock heterogeneity and saturation-dependent flow restrictions on cleanup efficiency. The results reveal that strong jail zones drastically hinder fracture fluid recovery, while weak jail configurations interact with heterogeneity to produce non-linear cleanup trends. Notably, reducing the pore size distribution index in Pc models improves predictive accuracy for ultra-tight conditions. These findings underscore the need to integrate unconventional Kr and Pc behaviour in hydraulic fracturing design to optimise flowback and long-term gas recovery. This work provides critical insights for improving reservoir performance and supports ambitions in energy resilience and net-zero transition strategies. Full article

We have previously shown that the mitochondrial respiratory chain (RC) can switch between the following two states: (i) an “ATP-producing” state characterized by the low production of reactive oxygen species (ROS), the vigorous translocation of hydrogen ions (H⁺), and the storage of energy from the H⁺ gradient in the form of ATP, and (ii) an “ROS-producing” state, where the translocation of H⁺ is slow but the production of ROS is high. Here, we suggest that the RC transition from an ATP-producing to an ROS-producing state initiates a mitochondrial permeability transition (MPT) by generating a burst of ROS. Numerous MPT activators induce the transition of the RC to an ROS-producing state, and the ROS generated in this state activate the MPT. The MPT, in turn, induces changes in conditions that are necessary for the RC to return to an ATP-producing state, decreasing the ROS production rate and restoring the normal permeability of the inner membrane. In this way, the transient MPT prevents cell damage from oxidative stress that would occur if the RC remained in an ROS-producing state. It is shown that an overload of glutamate, which enters through excitatory amino acid transporters (EAATs), induces the RC to switch to an ROS-producing state. Subsequent MPT activation causes a transition back to an ATP-producing state. The model was used to predict the spatial–temporal dynamics of glutamate concentrations and H₂O₂ production rates in a three-dimensional digital phantom of nervous tissue. Full article

The transition to a sustainable energy future hinges on the development of reliable large-scale hydrogen storage solutions to balance the intermittency of renewable energy and decarbonize hard-to-abate industries. Underground hydrogen storage (UHS) in salt caverns emerged as a technically and economically viable strategy, leveraging the unique geomechanical properties of salt formations—including low permeability, self-healing capabilities, and chemical inertness—to ensure safe and high-purity hydrogen storage under cyclic loading conditions. This review provides a comprehensive analysis of the advantages of salt cavern hydrogen storage, such as rapid injection and extraction capabilities, cost-effectiveness compared to other storage methods (e.g., hydrogen storage in depleted oil and gas reservoirs, aquifers, and aboveground tanks), and minimal environmental impact. It also addresses critical challenges, including hydrogen embrittlement, microbial activity, and regulatory fragmentation. Through global case studies, best operational practices for risk mitigation in real-world applications are highlighted, such as adaptive solution mining techniques and microbial monitoring. Focusing on China’s regional potential, this study evaluates the hydrogen storage feasibility of stratified salt areas such as Jiangsu Jintan, Hubei Yunying, and Henan Pingdingshan. By integrating technological innovation, policy coordination, and cross-sector collaboration, salt cavern hydrogen storage is poised to play a pivotal role in realizing a resilient hydrogen economy, bridging the gap between renewable energy production and industrial decarbonization. Full article

In order to clarify the feasibility of constructing a gas storage reservoir through synergistic injection and production in the target reservoir, micro-displacement experiments and multi-cycle injection–production experiments were conducted. These experiments investigated the displacement characteristics and the factors affecting storage capacity during the multi-cycle injection–production process for converting the target reservoir into a gas storage facility. Microscopic displacement experiments have shown that the remaining oil is primarily distributed in the dead pores and tiny pores of the core in the form of micro-bead chains and films. The oil displacement efficiency of water flooding followed by gas flooding is 18.61% higher than that of gas flooding alone, indicating that the transition from water flooding to gas flooding can further reduce the liquid saturation and increase the storage capacity space by 2.17%. Single-tube long-core displacement experiments indicate that, during the collaborative construction of a gas storage facility, the overall oil displacement efficiency without a depletion process is approximately 24% higher than that with a depletion process. This suggests that depletion production is detrimental to enhancing oil recovery and expanding the capacity of the gas storage facility. During the cyclic injection–production stage, the crude oil recovery rate increases by 1% to 4%. As the number of cycles increases, the incremental oil displacement efficiency in each stage gradually decreases, and so does the increase in cumulative oil displacement efficiency. Better capacity expansion effects are achieved when gas is produced simultaneously from both ends. Parallel double-tube long-core displacement experiments demonstrate that, when the permeability is the same, the oil displacement efficiencies during the gas flooding stage and the cyclic injection–production stage are essentially identical. When there is a permeability contrast, the oil displacement efficiency of the high-permeability core is 9.56% higher than that of the low-permeability core. The ratio of the oil displacement efficiency between the high-permeability end and the low-permeability end is positively correlated with the permeability contrast; the greater the permeability contrast, the larger the ratio. The research findings can provide a reference for enhancing oil recovery and expanding the capacity of the target reservoir when it is converted into a gas storage facility. Full article

Numerous uncertainties persist regarding the differential enrichment mechanisms of shale gas reservoirs in southern China. This investigation systematically examines the sedimentary environments and reservoir characteristics of the Wufeng–Longmaxi formations in the Changning area of the Sichuan Basin, through the integration of comprehensive drilling data, core samples, and analytical measurements. Multivariate sedimentary proxies (including redox conditions, terrigenous detrital influx, basinal water restriction, paleoclimatic parameters, paleowater depth variations, and paleo-marine productivity) were employed to elucidate environmental controls on reservoir development. The research findings demonstrate that during the depositional period of the Wufeng Formation in the Changning area, the bottom water was characterized by suboxic to anoxic conditions under a warm-humid paleoclimate, with limited terrigenous detrital input and strong water column restriction throughout the interval. Within the Longmaxi Formation, the depositional environment evolved from intensely anoxic conditions in the LM1 through suboxic states in the LM3 interval, approaching toxic conditions by the LM2 depositional phase. Concurrently, the paleoclimate transitioned towards warmer and more humid conditions, accompanied by progressively intensified terrigenous input from the LM1-LM6, while maintaining semi-restricted water circulation. Both paleowater depth and paleoproductivity peaked from the Wufeng Formation to the LM1 interval, followed by gradual shallowing of water depth and declining productivity during the LM3–LM6 depositional phases. Comparative analysis of depositional environments and reservoir characteristics reveals that sedimentary conditions exert a controlling influence on multiple reservoir parameters, including shale mineral composition, organic matter enrichment, pore architecture, petrophysical properties (e.g., porosity, permeability), and gas-bearing potential. Full article

Understanding nonlinear fluid flow in fractured rocks is critical for various geoengineering and geosciences. This study investigates the evolution of seepage behavior under varying fracture surface roughness, confining pressures, and shear displacements. A total of four sandstone fracture specimens were prepared using controlled splitting techniques, with surface morphology quantified by Joint Roughness Coefficient (JRC) values ranging from 2.8 to 17.7. Triaxial seepage tests were conducted under four confining pressures (3–9 MPa) and four shear displacements (0–1.5 mm). Experimental results reveal that permeability remains stable under low hydraulic gradients but transitions to nonlinear regimes as the flow rate increases, accompanied by significant energy loss and deviation from the cubic law. The onset of nonlinearity occurs earlier with higher roughness, stress, and displacement. A critical hydraulic gradient Jc was introduced to define the threshold at which inertial effects dominate. Forchheimer’s equation was employed to model nonlinear flow, and empirical regression models were developed to predict coefficients A, B, and Jc using hydraulic aperture and JRC as input variables. These models demonstrated high accuracy (R² > 0.92). This work provides theoretical insights and predictive approaches for assessing nonlinear fluid transport in rock fracture. Future research will address mechanical–hydraulic coupling and incorporate additional factors such as scale effects and flow anisotropy. Full article

Neurosteroids pregnenolone, progesterone, allopregnanolone, and dehydroepiandrosterone have been actively studied in the last years as candidates for the treatment of neurodegenerative diseases and postinjury rehabilitation. The neuroprotective mechanisms of these neurosteroids have been shown in clinical studies of depression, epilepsy, status epilepticus, traumatic brain injury, fragile X syndrome, and chemical neurotoxicity. However, only the allopregnanolone analogs brexanolone and zuranolone have been recently approved by the FDA for the treatment of depression. The aim of this review was to evaluate whether the endogenous neurosteroids can be used in clinical practice as neuroprotectors. Neurosteroids are multitarget compounds with strong anti-inflammatory, immunomodulatory, and cytoprotective action; they stimulate the synthesis and release of BDNF and increase remyelination and regeneration. In addition to nuclear and membrane steroid hormone receptors, such as PR, mPR, PGRMC1,2, ER, AR, CAR, and PXR, they can bind to GABAA receptors, NMDA receptors, Sigma-1 and -2 receptors (σ1-R/σ2-R). Among these, mPRs, PGRMC1,2, sigma receptors, and mitochondrial proteins attract comprehensive attention because of strong binding with the P4 and DHEA, but subsequent signaling is poorly studied. Other plasma membrane and mitochondrial proteins are involved in the rapid nongenomic neuroprotective action of neurosteroids. P-glycoprotein, BCL-2 proteins, and the components of the mitochondrial permeability transition pore (mPTP) play a significant role in the defense against the injuries of the brain and the peripheral nervous system. The role of these proteins in the molecular mechanisms of action in neuroprotection and neuroinflammation has not yet been clearly established. The aspects of their participation in these pathological processes are discussed. New formulations, such as lipophilic emulsions, nanogels, and microneedle array patches, are attractive strategies to overcome the low bioavailability of these neurosteroids for the amelioration and treatment of various nervous disorders. Full article

The development of shale bedding and fractures exacerbates the invasion of drilling fluid, leading to significant reservoir damage. This article elucidates the strength degradation behavior of shale with bedding orientations of 0° and 90° under drilling fluid immersion, as determined through triaxial compression experiments. An improved Hooke–Brown anisotropic strength criterion has been established to quantitatively characterize the degradation effects. Additionally, a dynamic mechanism of pore pressure accumulation was simulated. The research findings indicate the following: (1) As the intrusion pressure increases from 6 MPa to 8 MPa, the penetration depth significantly increases. In the horizontal bedding direction (0°), cracks dominate the flow mode, resulting in a sudden drop in strength; (2) An increase in bedding density or opening exacerbates the degree of invasion and strength degradation in the horizontal bedding direction, with a degradation rate exceeding 40%. In contrast, the vertical bedding direction is influenced by permeability anisotropy and crack blockage, leading to limited seepage and minimal degradation. By optimizing the dosage of emulsifiers and other treatment agents through orthogonal experiments, a low-viscosity, high-shear-strength plugging oil-based drilling fluid system was developed, effectively reducing the invasion depth of the drilling fluid by over 30%. The primary innovations of this article include the establishment of a quantitative model for Reynolds number degradation for the first time, which elucidates the mechanism of accelerated crack propagation during turbulent transition (when the Reynolds number exceeds the critical value of 10). Additionally, a novel method for synergistic control between sealing and rheology is introduced, significantly decreasing the degradation rate of horizontal bedding. Furthermore, the development of the Darcy–Forchheimer partitioning algorithm addresses the issue of prediction bias exceeding 15% in high-Reynolds-number regions (Re > 30). The research findings provide a crucial theoretical foundation and data support for the optimized design of drilling fluids. Full article

Background: The rise in multidrug-resistant bacteria has intensified the search for new antibiotics, drawing attention to essential oils (EOs) for their antimicrobial properties. For this reason, this study focuses on the antimicrobial action of the EO obtained from Tagetes minuta and its impact on bacterial membranes. Methods: The EO was chemically characterized by chromatography–mass spectrometry, and its antimicrobial activity and its effects on surface and bacterial membrane were assessed by using Zeta potential, membrane transition temperature (Tm) determination; and fluorescence spectroscopy with Laurdan and Di-8 ANEPPS. Results: Twenty-seven compounds could be identified, with (E)-Tagetone, (Z)-Ocimenone, and β-pinene as the most abundant. Afterward, the EO was tested against Escherichia coli (MIC and MBC = 17 mg/mL) and Staphylococcus aureus (MIC = 8.5 mg/mL; MBC > 17 mg/mL), showing antimicrobial action in both bacteria, being more effective against E. coli. Mechanistic studies revealed that the EO interacts with bacterial membranes, increasing the Zeta potential by more than 9 mV and enhancing membrane permeability up to 90%. These effects were further confirmed using model lipid membranes, where the EO induced significant changes in membrane properties, including a reduction in dipole potential and transition temperature, suggesting that some EO components could be inserted into the lipid bilayer, disrupting membrane integrity. Conclusions: The EO from T. minuta demonstrates efficient antimicrobial activity by compromising bacterial membrane structure, highlighting its potential as a natural antimicrobial agent. Full article

Background: Tariquidar (Tq) is an inhibitor of the multidrug resistance (MDR) proteins relevant to ATP-binding cassette transporters (ABC transporters), which suppresses the ATP-dependent efflux of a variety of hydrophilic and amphipathic compounds, including anticancer drugs. Tq is a representative of a new generation of MDR inhibitors with high affinity to ABC proteins. However, there are still no data on the possible effect of Tq on mitochondria as an important target in the regulation of cell death or survival. Methods: We investigated the influence of Tq on the Ca²⁺-dependent mitochondrial permeability transition pore (mPTP). The effect of Tq was assessed using several parameters, including the calcium load, membrane potential, and mitochondrial swelling. To evaluate the specific targets of Tq, selective inhibitors of components of the mitochondrial pore were used, including adenine nucleotides, carboxyatractylozide (Catr) and bongkrekic acid (BA), oligomycin, and cyclosporine A. Results: Tq decreased the calcium retention capacity, activated mitochondrial swelling, and lowered the influence of ADP and ATP, the inhibitors of the Ca²⁺-induced pore opening, at their low concentrations. These effects of Tq were observed in both calcium-load and swelling assays, thus mimicking the effect of Catr, a selective inhibitor of adenine nucleotide translocase (ANT). Tq also decreased the protective effect of BA, an inhibitor of ANT and mPTP, on the calcium retention capacity of mitochondria. Further, Tq dose-dependently decreased the inhibitory effect of a low ATP concentration but not of high concentrations, at which the effect of Tq was activated by oligomycin, an inhibitor of F-ATP synthase. Conclusions: The influence of Tq extends to mitochondria, specifically to the regulation of membrane permeability, promoting the activation of pore opening, probably through an interaction with ANT, a component of the pore-forming complex. The effect of Tq on the opening of mPTP is strongly dependent on the concentrations of adenine nucleotides and, consequently, on the functional state of mitochondria. The direct influence of Tq on mitochondria can be considered as a new activity that promotes the sensitization of cells to various treatments and stimuli. Full article

The saiga antelope (Saiga tatarica), a keystone migratory species of the Central Asian steppes and deserts, is increasingly threatened by habitat fragmentation due to the rapidly expanding transport infrastructure in Kazakhstan, which hosts approximately 95% of the species’ global population. This study provides a spatial assessment of railway and road infrastructure across the contemporary ranges of the Betpaqdala, Ustyurt, and Ural saiga populations. Using the literature and our field data from the 1980s to the present day, combined with geographic information system (GIS)-based analysis of 80,427 km of roads and 4021 km of railways, we have quantified infrastructure densities and identified critical barriers to saiga migration using kernel density and minimum convex polygons (MCP) estimations. The results reveal a negative connection between infrastructure density and occurrences of saiga herds, particularly in the Ustyurt population, where a high railway density coincides with severely reduced migratory activity and a reduction in this population’s winter range by 79.84% since 2015. Major railways such as Sekseuildi–Zhezqazgan, Zhezqazgan–Zharyk, and Shalqar–Beineu intersect essential migratory pathways and have contributed to significant range contraction, subpopulation isolation, and northward shifts in seasonal habitats. In contrast, the Ural population (subject to minimal railway infrastructure interference) has shown robust demographic recovery. While roads are more widespread, their impact is less severe due to greater permeability. However, upcoming projects such as the China–Europe transit corridor and the “Center–West” regional development corridor could amplify future threats. We recommend immediately implementing wildlife-friendly infrastructure, including overpasses and ecological corridors, to preserve the connectivity of saiga ranges and support the long-term conservation of this ungulate species. Full article

Organic framework membranes (OFMs) have emerged as transformative materials for separation technologies due to their tunable porosity, structural diversity, and stability, yet their design and optimization face challenges in navigating vast chemical spaces and complex performance trade-offs. This review highlights the pivotal role of machine learning (ML) in overcoming these limitations by integrating multi-source data, constructing quantitative structure–property relationships, and enabling the cross-scale optimization of OFMs. Methodologically, ML workflows—spanning data construction, feature engineering, and model optimization—accelerate candidate screening, inverse design, and mechanistic interpretation, as demonstrated in gas separations and nascent liquid-phase applications. Key findings reveal that ML identifies critical structural descriptors and environmental parameters, guiding the development of high-performance membranes that surpass traditional selectivity–permeability limits. Challenges persist in liquid separations due to dynamic operational complexities and data scarcity, while emerging frameworks offer untapped potential. The integration of interpretable ML, in situ characterization, and industrial scalability strategies is essential to transition OFMs from laboratory innovations to sustainable, adaptive separation systems. This review underscores ML’s transformative capacity to bridge computational insights with experimental validation, fostering next-generation membranes for carbon neutrality, water security, and energy-efficient industrial processes. Full article

A generalized model of the variable permeability in the transition layer is introduced in this work. This model can handle flows with a small Darcy number and might be useful in controlling permeability amplifications. A solution method for the resulting inhomogeneous, generalized Airy equation is presented, together with a computational procedure for evaluating the generalized Airy functions and the generalized Nield–Kuznetsov function of the first kind. A complete solution is then provided for the tri-layer flow problem that involves flow over a porous layer with an embedded transition layer. Full article