Search Results (101)

Background/Objectives: The novel compound 221s (2,9), derived from danshensu and ACEI-active proline, exhibits antihypertensive effects (50/35 mmHg SBP/DBP reduction in SHRs) with potential cough mitigation. However, its excretion kinetics remain unstudied. This study investigates 221s (2,9) elimination in rats to bridge this knowledge gap. Methods: Excretion of unchanged 221s (2,9) was quantified in urine, feces, and bile of Sprague-Dawley rats after oral administration (30 mg/kg). Concentrations of unchanged 221s (2,9) in all matrices were quantified using developed UPLC-MS/MS that underwent methodological validation. Excretion amount, excretion velocity, and accumulative excretion rate of 221s (2,9) were calculated. Results: Urinary excretion exhibited rapid elimination kinetics, reaching peak cumulative excretion rates (138.81 ± 15.56 ng/h) at 8 h post-dosing and plateauing by 48 h (cumulative excretion: 1479.81 ± 155.7 ng). Fecal excretion displayed an accelerated elimination phase between 4 and 8 h (excretion rate: 7994.29 ± 953.75 ng/h), followed by a sustained slow-release phase, culminating in a cumulative output of 36,726.31 ± 5507 ng at 48 h. Biliary excretion was minimal and ceased entirely by 24 h. Notably, total recovery of unchanged drug across all matrices remained below 1% (urine: 0.020 ± 0.021%; feces: 0.73 ± 0.069%; bile: 0.00044 ± 0.00002%) at 72 h. Conclusions: This study provides the first definitive excretion data for 221s (2,9). Quantitative analysis via a validated UPLC-MS/MS method revealed that fecal excretion is the principal elimination pathway for unchanged 221s (2,9) in rats, with direct excretion of the parent compound accounting for <1% of the administered dose over 72 h. Future studies will employ extended pharmacokinetic monitoring and concurrent UPLC-MS/MS analysis of the parent drug and phase II conjugates to resolve the observed mass imbalance and elucidate contributions to total elimination. Full article

Natural gas hydrates (NGHs) are promising energy resources, although their marine exploitation is limited by low reservoir permeability and hydrate decomposition efficiency. Multi-cluster fracturing technology can enhance reservoir permeability, yet complex properties of hydrate sediments render the prediction of fracture behavior challenging. Therefore, we developed a three-dimensional (3D) fluid–solid coupling model for hydraulic fracturing in NGH reservoirs based on cohesive elements to analyze the effects of sediment plasticity, hydrate saturation, fracturing fluid viscosity, and injection rate, as well as the stress interference mechanisms in multi-cluster simultaneous fracturing under different cluster spacings. Results show that selecting low-plastic reservoirs with high hydrate saturation (S_H > 50%) and adopting an optimal combination of fracturing fluid viscosity and injection rate can achieve the co-optimization of stimulated reservoir volume (SRV) and cross-layer risk. In multi-cluster fracturing, inter-fracture stress interference promotes the propagation of fractures along the fracture plane while suppressing it in the normal direction of the fracture plane, and this effect diminishes significantly till 9 m cluster spacing. This study provides valuable insights for the selection of optimal multi-cluster fracturing parameters for marine NGH reservoirs. Full article

Deepwater natural gas hydrate (NGH) exploration faces environmental and economic challenges due to the conventional seabed discharge of drilling mud. To address this, we developed an improved riserless mud recovery (RMR) system using hybrid risers to create a stable, decoupled circulation pathway. This innovative design fulfils three key operational needs: (1) closed-loop drilling fluid circulation with dual-gradient control, (2) completion fluid and test production returns, and (3) mechanical decoupling between the floating platform and subsea riser string. Numerical analysis shows that the system maintains operational stability under wave loading while effectively isolating seabed equipment from platform motion. Simulation results indicate that optimal performance requires a top tension ratio exceeding 1.5 and a submersion depth of 150–250 m, achieving a 70–80% reduction in drilling fluid consumption with full recovery capabilities. The hybrid riser-based RMR system provides a practical solution for sustainable NGH development, offering superior water depth adaptability for both drilling and completion operations in deepwater environments. Full article

The efficient extraction of natural gas from marine natural gas hydrate (NGH) reservoirs is challenging, due to their low permeability, high hydrate saturation, and fine-grained sediments. Hydraulic fracturing has been proven to be a promising technique for improving the permeability of these unconventional reservoirs. This study presents a comprehensive triaxial experimental investigation of the fracturing behavior and fracture initiation mechanisms of NGH-bearing sediments, using large-scale ice-saturated synthetic cubic models. The experiments systematically explore the effects of key parameters, including the injection rate, fluid viscosity, ice saturation, perforation patterns, and in situ stress, on fracture propagation and morphology. The results demonstrate that at low fluid viscosities and saturation levels, transverse and torsional fractures dominate, while longitudinal fractures are more prominent at higher viscosities. Increased injection rates enhance fracture propagation, generating more complex fracture patterns, including transverse, torsional, and secondary fractures. A detailed analysis reveals that the perforation design significantly influences the fracture direction, with 90° helical perforations inducing vertical fractures and fixed-plane perforations resulting in transverse fractures. Additionally, a plastic fracture model more accurately predicts fracture initiation pressures compared to traditional elastic models, highlighting a shift from shear to tensile failure modes as hydrate saturation increases. This research provides new insights into the fracture mechanisms of NGH-bearing sediments and offers valuable guidance for optimizing hydraulic fracturing strategies to enhance resource extraction in hydrate reservoirs. Full article

Leptin-deficient (ob/ob) and leptin receptor (Lepr)-deficient db/db mice develop a mild form of osteoclast-rich osteopetrosis, most evident in long bone epiphyses, implying leptin is important for normal replacement of cartilage during skeletal maturation. However, it is unclear whether leptin acts as a permissive or regulatory factor and whether its actions are mediated via peripheral pathways. Here we show the osteopetrotic phenotype is not evident in ob/+ or db/+ mice, suggesting that leptin acts as a critical but permissive factor for skeletal maturation. The importance of leptin is further supported by our results showing that interventions known to increase bone resorption (mild cold stress, simulated microgravity, or particle-induced inflammation) did not advance skeletal maturation in ob/ob mice whereas long-duration hypothalamic leptin gene therapy was effective. Additionally, administration of leptin by subcutaneously implanted osmotic pumps (400 ng/h) for 2 weeks accelerated skeletal maturation in ob/ob mice. Because leptin has the potential to act on the skeleton through peripheral pathways, we interrogated osteoclast-lineage cells for the presence of Lepr and evaluated skeletal response to the introduction of bone marrow Lepr⁺ cells into db/db mice. We identified Lepr on marrow MCSFR⁺CD11b⁺ osteoclast precursors and on osteoclasts generated in vitro. We then adoptively transferred Lepr⁺ marrow cells from GFP mice or wildtype (WT) mice into Lepr^- db/db mice. Following engraftment, most MCSFR⁺ CD11b⁺ cells in marrow expressed GFP. Whereas db/db→db/db had minimal influence on epiphyseal cartilage, WT→db/db decreased cartilage. These findings suggest peripheral leptin signaling is required for normal osteoclast-dependent replacement of cartilage by bone during skeletal maturation. Full article

Natural gas hydrate (NGH hereafter), commonly known as combustible ice ((CH₄)n·mH₂O), is an abundant non-conventional clean energy resource. It is mainly located in permafrost areas and submarine sediment layers at depths of 0–200 m and 300~3000 m underwater. Submarine NGH accounts for about 97%. Its commercial mining may be a solution to mankind’s future energy problems, as well as the beginning of a series of geological risks. These risks can be divided into two categories: natural geological hazards and secondary geological accidents. Based on the viewpoints of Earth system science researchers, this paper discusses the main potential geo-hazards of submarine NGH mining: stratum subsidence, seafloor landslides, the greenhouse effect, sand piping, well blowout, and wellbore instability. To minimize the potential catastrophic impacts on the Earth’s ecosystem or mechanical accidents, corresponding technical precautions and policy suggestions have been put forward. Hopefully, this paper will provide a useful reference for the commercial mining of NGH. Full article

Background: The interaction and co-evolution between the gut microbiome and the host play important roles in the host’s physiology, nutrition, and health. Diet is considered an important driver of differences in the gut microbiota; however, research on the relationship between the gut microbiota and diet in Asian elephants remains limited. Methods: In this study, we explored the gut microbiota structure and its relationship with diet in different populations of Asian elephants through metagenomic sequencing, combined with previously published dietary data. Results: This study found that the dominant gut microbiota of Asian elephants includes the phyla Bacillota (29.85% in BP, 22.79% in RC, 21.89% in SM, 31.67% in ML, and 33.00% in NGH), Bacteroidota (25.25% in BP, 31.44% in RC, 16.44% in SM, 25.73% in ML, and 23.74% in NGH), and Spirochaetota (3.49% in BP, 6.18% in RC, 1.71% in SM, 2.69% in ML, and 3.52% in NGH), with significant differences in the gut microbiota among different populations. Correlation analysis between the gut microbiota and diet revealed that dietary diversity did not directly affect the alpha diversity of the gut microbiota. However, specific food types might play a key role in shaping the gut microbiota structure by regulating the abundance of certain microbiota. Conclusions: This study reveals significant differences in the gut microbiota structure among different populations of Asian elephants and explores the impact of diet on the structure. The results provide foundational data for a deeper understanding of the gut microbiota structure of Asian elephants and offer important references for the scientific conservation and precise management strategies of this species. Full article

In this study, we provide the first estimates of the effect of COVID-19 (COVID-19 legal restrictions) on catastrophic medical expenditure and forgone medical care in Africa. Data for this study were drawn from the 2018/19 Nigeria General Household Survey (NGHS) panel and the 2020/21 Nigeria COVID-19 National Longitudinal Phone Survey panel (COVID-19 NLPS). The 2020/21 COVID-19 panel survey sample was drawn from the 2018/19 NGHS panel sample monitoring the same households. Hence, we leveraged a rich set of pre-COVID-19 and COVID-19 panel household surveys that can be merged to track the effect of the pandemic on welfare outcomes. We found that the COVID-19 legal restrictions decreased catastrophic medical expenditure (measured by out-of-pocket (OOP) expenditures exceeding 10% of total household expenditure). However, the COVID-19 legal restrictions increased the incidences of forgone medical care. The results showed a consistent positive effect on forgone medical care across waves one and two, corresponding to full and partial implementation of COVID-19 legal restrictions, respectively. However, the negative effect on catastrophic medical spending was only observed when the COVID-19 legal restrictions were fully in force, but the sign reversed when the restriction enforcement became partial. Moreover, our panel regression analyses revealed that having health insurance is associated with a reduced probability of incurring CHE and forgoing medical care relative to having no health insurance. We suggest that better policy design in terms of expanding the depth and coverage of health insurance will broaden access to quality healthcare services during and beyond the pandemic periods. Full article

Natural gas hydrate (NGH) is a clean resource characterized by abundant potential reserves, clean combustion, and high energy density. Although significant progress has been made in the development of NGH resources all around the world, challenges still exist that hinder commercial exploitation, such as a low daily gas production rate and short steady production periods. One significant reason lies in the complex gas–liquid–solid phase transitions occurring within the formation during production, which lead to changes in flow capacity. Understanding the phase change mechanism of NGH reservoirs will help to further reveal the production increase mechanism. To address the phase transitions’ effect on production, this paper establishes a numerical simulation model for the depressurization exploitation of natural gas hydrates in order to investigate phase transition characteristics at the field scale. First, the phase equilibrium calculation method is presented and the phase equilibrium curve is modified by considering the capillary effect, soluble salt, and surface adsorption. Then, the phase transition model is successfully characterized in a simulation and the numerical simulation model is established based on the first test project parameters in the Shenhu area. The production characteristics of different sediment types (montmorillonite, South China Sea sediments, kaolin, and silt) are analyzed under the effects of water content and salinity. It is shown that lower initial water content and higher salinity result in higher gas production. The results provide a better understanding of the effects of phase transition parameters on NGH production at the field scale. Full article

In response to escalating global energy demand and climate change mitigation needs, natural gas hydrates (NGHs) are gaining prominence as a clean energy source. The CO₂ replacement method is an innovative NGH extraction technique that reduces reservoir risks and enables CO₂ sequestration. However, our understanding of the dynamics and control parameters in the hydrate replacement process is limited. This study pioneers a kinetic analysis and conceptual model for a CO₂-driven hydrate replacement, dividing the process into three spatial realms and sequential stages. We identify the optimal injection temperature range for standard NGH reservoirs and highlight the interplay between the gas injection rate and bottom-hole pressure on CH₄ yield. Our findings offer insights on how to optimize production efficiency and gas separation, advancing CO₂ replacement technology for NGHs. Full article

Background: Morphine analgesic tolerance (MAT) limits the clinical application of morphine in the management of chronic pain. IIK7 is a melatonin type 2 (MT2) receptor agonist known to have antioxidant properties. Oxidative stress is recognized as a critical factor in MAT. This study sought to assess the impact of IIK7 on the progression of MAT and its potential to reverse pre-existing MAT. Methods: Wistar rats underwent partial sciatic nerve transection (PSNT) surgery to induce neuropathic pain (NP). Seven days post nerve transection, we implanted an intrathecal (i.t.) catheter and linked it to an osmotic pump. Rats were randomly divided into the following groups: sham-operated/vehicle, PSNT/vehicle, PSNT/IIK7 50 ng/h, PSNT/MOR 15 g/h, and PSNT/MOR 15 g + IIK7 50 ng/h. We implanted two i.t. catheters for drug administration and the evaluation of the efficacy of IIK7 in reversing pre-established MAT. We linked one to an osmotic pump for MOR or saline continuous i.t. infusion. On the 7th day, the osmotic pump was disconnected, and 50 μg of IIK7 or the vehicle was administered through the second catheter. After 3 h, 15 μg of MOR or saline was administered, and the animal behavior tests were performed. We measured the levels of mRNA for Nrf2 and HO-1, pro-inflammatory cytokines (PICs), and the microglial and astrocyte activation in the spinal cord. Results: The co-administration of IIK7 with MOR delayed MAT development in PSNT rats by restoring Nrf2 and HO-1 while also inhibiting the microglial-cell and astrocyte activation, alongside the suppression of PICs. Additionally, a single injection of high-dose 50 μg IIK7 was efficient in restoring MOR’s antinociception in MOR-tolerant rats. Conclusions: Our results indicate that the co-infusion of ultra-low-dose IIK7 can delay MAT development and a high dose can reverse pre-existing MAT. Full article

Three-dimensional geological modeling is essential for simulating natural gas hydrate (NGH) productivity and formulating development strategies. Current approaches primarily concentrate on the single-phase modeling of either hydrate or free gas layers. However, an increasing number of instances suggest that the three-phase coexistence zone, which includes hydrate, gas, and water, is common and has become a focal point of international research, as this type of reservoir may present the most viable opportunities for exploitation. At present, there exists a significant gap in the research regarding modeling techniques for such reservoirs. This study undertakes a comprehensive modeling investigation of the three-phase zone reservoir situated in the sand layer of the Qiongdongnan Basin. By employing deterministic complex geological modeling techniques and integrating existing seismic and logging data, we have developed a three-phase coexistence zone model that precisely characterizes the interactions between geological structures and utilizes them as auxiliary constraints. This approach effectively mitigates the potential impact of complex geological conditions on model accuracy. Through a comprehensive analysis of 105 seismic profiles, we enhanced the model’s accuracy, resulting in the creation of a three-phase coexistence zone model comprising 350,000 grids. A comparison between the modeling results and well data indicates a relatively small error margin, offering valuable insights for future development efforts. Furthermore, this method serves as a reference for modeling hydrates in marine environments characterized by three-phase coexistence on a global scale. Full article

Natural gas hydrates (NGHs) in the Shenhu area of the South China Sea are deposited in low-permeability clayey silt sediments. As a renewable energy source with such a low carbon emission, the exploitation and recovery rate of NGH make it difficult to meet industrial requirements using existing development strategies. Research into an economically rewarding method of gas hydrate development is important for sustainable energy development. Hydraulic fracturing is an effective stimulation technique to improve the fluid conductivity. In this paper, an efficient three-dimensional embedded discrete fracture model is developed to investigate the production simulation of hydraulically fractured gas hydrate reservoirs considering the stimulated reservoir volume (SRV). The proposed model is applied to a hydraulically fractured production evaluation of vertical wells, horizontal wells, and complex structural wells. To verify the feasibility of the method, three test cases are established for different well types as well as different fractures. The effects of fracture position, fracture conductivity, fracture half-length, and stimulated reservoir volume size on gas production are presented. The results show that the production enhancement in multi-stage fractured horizontal wells is obvious compared to that of vertical wells, while spiral multilateral wells are less sensitive to fractures due to the distribution of wellbore branches and perforation points. Appropriate stimulated reservoir volume size can obtain high gas production and production efficiency. Full article

Depressurization combined with heat (mainly hot water) injection is an important technique for exploiting natural gas hydrate (NGH). To overcome the problems of pore water intrusion and hot water energy loss in the technique, this paper employs a method of setting sealing boundaries in permeable overburden and underburden to exploit NGH. The influence of the presence of sealing boundaries on NGH exploitation performances was numerically investigated. The results indicate that the sealing boundaries in permeable overburden and underburden can inhibit water intrusion and reduce heat loss, significantly improving the efficiency of hydrate dissociation and gas production. Specifically, the hydrate dissociation and gas production efficiency increased by 22.0–30.1% and 63.9–85.1%, respectively. Moreover, there is an optimal sealing vertical distance within the range of 0–15 m, maximizing the mining efficiency of NGH at the end of production. On the other hand, the presence of sealing boundaries effectively limits the escape range of CH₄ in the permeable overburden and underburden, resulting in an increasing gas-to-water ratio and an increasing energy efficiency. These findings provide theoretical and technical support for the mining of NGH by depressurization combined with heat injection. Full article

As one of the most important future clean energy sources, natural gas hydrate (NGH) is attracting widespread attention due to the vast reserves available and high energy density. How to extract this source in a safe, efficient, and environmentally friendly manner has become the key to the commercial utilization of its resources. This paper reviews the recent advances in the study of the fundamental reservoir properties of offshore NGH, summarizing the methods and technologies for testing the sedimentary properties of reservoirs, analyzing the characteristics in reservoir mechanics, electrics, thermodynamics, and fluid dynamics, and discusses the influence of reservoir fundamental properties on NGH exploitation. The aim is to provide guidance and reference for research on the exploitation of NGH in different target exploitation areas offshore. Full article