Sirt3 Ameliorates Oxidative Stress and Mitochondrial Dysfunction After Intracerebral Hemorrhage in Diabetic Rats

Aim: Sirtuin3 (sirt3) plays a pivotal role in improving oxidative stress and mitochondrial dysfunction which directly induced neuronal apoptosis after intracerebral hemorrhage (ICH). Reactive oxygen species (ROS) is also a critical activator in triggering NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasomes activation which can regulate inflammatory responses in brain. Moreover, hyperglycemia can aggravate the ICH-induced damage. Hence, this study was designed to investigate the mechanisms of neuroprotection of sirt3 in hyperglycemic ICH.Methods: ICH model was established by autologous blood injection. Hyperglycemia was induced by intraperitoneal injection with streptozotocin. Honokiol (HKL, a pharmacological agonist of sirt3) was injected intraperitoneally at doses of 2.5, 5, or 10 mg/kg. Sirt3 small interfering RNA transfection was implemented through intracerebroventricular injection. The expression of sirt3 and its downstream signaling molecules were detected using Western blotting or immunofluorescence staining. Morphological changes of mitochondria were detected by electron microscopy. SH-SY5Y cells were incubated with 10 μM oxyhemoglobin for 48 h to establish an in vitro ICH model, and then JC-1 staining was used to determine mitochondrial membrane potential (Δψm).Results: Hyperglycemia could suppress sirt3 expression after ICH when compared with non-diabetic rats. Sirt3 protein expression was decreased to the minimum at 24 h in perihematoma tissues. Electron microscope analysis indicated that hyperglycemic ICH induced extensive mitochondrial vacuolization. HKL attenuated ROS accumulation, adenosine triphosphate reduction, and Δψm through Sirt3–superoxide dismutase 2 (SOD2) and Sirt3–NRF1–TFAM pathway. Sirt3 knockdown could exacerbate the neuronal apoptosis and reverse the positive effects of HKL. Sirt3 activation could decrease NLRP3 and interleukin-1β levels through deacetylating SOD2 and scavenging ROS.Conclusion: HKL protects against hyperglycemic ICH-induced neuronal injury via a sirt3-dependent manner

Inventory forecast of underground gas storage based on modified material balance equation

In view of the gap between the gas storage inventory forecasted by the traditional material balance equation and the actual inventory, experiments of displacing gas by water and displacing water by gas were carried out, and the modified material balance equation considering pore volume loss due to water invasion and pay heterogeneity was deduced based on the percolation mechanism inferred from the experiments above, moreover the equation was verified by example analysis. The experimental results show that: the irreducible water saturation and residual gas saturation in underground gas storage (UGS) domain should be evaluated through water-gas seepage experiments because these parameters are different from the process of gas field development; the pore volume in the water flooded reservoir decreases after conversion for gas storage, and the pore volume loss increases rapidly when the reservoir permeability decreases. The net pay was divided into flooded zone, transitional zone and gas zone with the equations for pore volume loss calculating due to water flooded. Then one parameter describing reservoir heterogeneity was defined based on numerical simulation and eventually the traditional material balance equation was modified with the consideration of pore volume loss due to water invasion and reservoir heterogeneity. Example analysis result shows that the actual UGS inventory differs greatly from the inventory predicted by the traditional material balance equation, but agrees with that calculated by the modified one. Key words: underground gas storage, inventory, material balance equation, reservoir water invasion, pore volume, heterogeneit

Recent Advances of the NLRP3 Inflammasome in Central Nervous System Disorders

Inflammasomes are multiprotein complexes that trigger the activation of caspases-1 and subsequently the maturation of proinflammatory cytokines interleukin-1β and interleukin-18. These cytokines play a critical role in mediating inflammation and innate immunity response. Among various inflammasome complexes, the NLRP3 inflammasome is the best characterized, which has been demonstrated as a crucial role in various diseases. Here, we review recently described mechanisms that are involved in the activation and regulation of NLRP3 inflammasome. In addition, we summarize the recent researches on the role of NLRP3 inflammasome in central nervous system (CNS) diseases, including traumatic brain injury, ischemic stroke and hemorrhagic stroke, brain tumor, neurodegenerative diseases, and other CNS diseases. In conclusion, the NLRP3 inflammasome may be a promising therapeutic target for these CNS diseases

Injection–production mechanisms and key evaluation technologies for underground gas storages rebuilt from gas reservoirs

Underground gas storages (UGSs) rebuilt from gas reservoirs is the most popular UGS type in the world. It accounts for 75% of the total active gas of all gas storages. In order to design more scientific and reliable geological schemes for constructing the underground gas storages rebuilt from gas reservoirs and optimize the UGS operation parameters, we analyzed the UGS basic characteristics of multi-cycle high-rate injection and production. Then, the dynamic sealing capacity of traps and the water–gas high-speed interactive flow mechanism of UGSs rebuilt from gas reservoirs with complex geological conditions were investigated by both physical simulation and numerical simulation. Finally, the key technologies for evaluating the dynamic sealing capacity of caprocks and faults and the storage capacity parameters were developed. Some results were obtained. First, the alternating stress in the process of UGS injection and production weakens the original static capillary sealing capacity and mechanical integrity of caprocks to different extents, and the trap sealing capacity can be quantified and evaluated comprehensively by using dynamic breakthrough pressures, shear safety indexes and other indicators. Second, a UGS capacity design method based on effective gas-bearing pores was developed according to the local pore-based recovery mechanism revealed in the high-speed gas–water mutual flooding test. Field application in the multi-layer UGS of H shows that these technologies provide an effective guidance for the design of geologic schemes. After five cycles of injection and production, its ramp-up ratio reached 91.8% and the peak shaving capacity increased quickly to 36.3 × 108 m3 from 2.7 × 108 m3 in the early stage of production. Moreover, the operation indicators matched well with the design. Keywords: Underground gas storage rebuilt from gas reservoir, Production mode, Operation law, Dynamic sealing capacity of trap, Evaluation index, Injection–production mechanism, Injector–producer flow, Storage capacity paramete

A High-Throughput Search for Composition–Phase–Property Relations of Cu–Ni/Ti–Al Elastic Copper Alloys

A high-throughput method was employed to effectively obtain the cross-scale relationship of elastic copper alloys. Firstly, a Cu⁻Ni⁻Ti⁻Cu25Al⁻Cu35Sn diffusion multiple was prepared and heat-treated under a specified condition to form a series of diffusion layers with the concentration gradient at the multielement metal interface. Then, the compositions, elastic moduli, and hardness of the Cu⁻Ni⁻Al and Cu⁻Ti⁻Al ternary copper alloys were tested. Meanwhile, the solid phase sequences in the diffusion zones were predicted by the CALPHAD (CALculation of PHAse Diagram) method. Through these experimental and calculated results, the composition⁻phase⁻property relations of the Cu⁻Ni⁻Al and Cu⁻Ti⁻Al ternary systems were established

Key evaluation techniques in the process of gas reservoir being converted into underground gas storage

Abstract: Due to the significant differences in development modes and operation rules of underground gas storage (UGS) and gas reservoir, the design of UGS construction has its own particularity and complexity. Key evaluation techniques in the process of gas reservoir being converted into underground gas storage were proposed and field application was analyzed. The construction and operation experience of the first batch commercial UGS in China was summarized, the mechanisms of multi-cycle injection and production with large flux in short-term was examined and some concepts were proposed such as the dynamic sealing of traps, the effective pore volume of UGS and the high velocity unstable seepage flow with finite supply. Four key technologies of UGS, i.e., trap sealing evaluation, gas storage parameter design, well pattern optimization and monitoring programs design were created. Preservation condition, storage capacity, effective injection & production and safe operation technology problems of UGS were solved respectively. The geological program design technology system of UGS construction in a gas field was gradually enriched and improved. These technologies have successfully guided geological plan design and implementation of UGS construction in a gas reservoir, the effects of gas storage and peaking capacity of the ramp-up cycles were great, and the actual dynamic was very consistent with design indicators. Key words: underground gas storage in gas field, dynamic sealing, gas storage parameter, productivity evaluation, injection-production well pattern, monitor schem

Melatonin Regulates Apoptosis and Autophagy Via ROS-MST1 Pathway in Subarachnoid Hemorrhage

Compelling evidence has indicated that imbalance between apoptosis and autophagy may be involved in subarachnoid hemorrhage (SAH). We aimed to investigate the effects and mechanisms of melatonin in the homeostasis of apoptosis and autophagy. One-hundred and forty-eight male Sprague-Dawley rats were intraperitoneally injected with melatonin or vehicle 2 h after SAH induction. Western blotting and an immunofluorescent assay were performed to detect the expression of apoptosis- and autophagy-related proteins. The neuroprotective effect of melatonin attenuating SAH-induced neurological deficit and brain edema may be associated with the suppression of SAH-induced neuronal apoptosis and autophagy. Furthermore, melatonin inhibited the cleavage of mammalian sterile 20-like kinase 1 (MST1) protein by reducing reactive oxygen species (ROS) content. These effects of melatonin on regulating the homeostasis between apoptosis and autophagy could be reversed by an MST1 agonist, chelerythrine, via enhancement of MST1 cleavage. In conclusion, exogenous melatonin alleviates SAH-induced early brain injury (EBI) by suppressing excessive neuronal apoptosis and autophagy. The underlying mechanism may, at least in part, involve the ROS-MST1 pathway