Numerical study on gas production via a horizontal well from hydrate reservoirs with different slope angles in the South China Sea

It is important to study the effect of hydrate production on the physical and mechanical properties of low-permeability clayey–silty reservoirs for the largescale exploitation of hydrate reservoirs in the South China Sea.In this study,a multiphysical-field coupling model,combined with actual exploration drilling data and the mechanical experimental data of hydrate cores in the laboratory,was established to investigate the physical and mechanical properties of low-permeability reservoirs with different slope angles during 5-year hydrate production by the depressurization method via a horizontal well.The result shows that the permeability of reservoirs severely affects gas production rate,and the maximum gas production amount of a 20-m-long horizontal well can reach186.8 m3/day during the 5-year hydrate production.Reservoirs with smaller slope angles show higher gas production rates.The depressurization propagation and hydrate dissociation mainly develop along the direction parallel to the slope.Besides,the mean effective stress of reservoirs is concentrated in the near-wellbore area with the on-going hydrate production,and gradually decreases with the increase of the slope angle.Different from the effective stress distribution law,the total reservoir settlement amount first decreases and then increases with the increase of the slope angle.The maximum settlement of reservoirs with a 0°slope angle is up to 3.4 m,and the displacement in the near-wellbore area is as high as2.2 m after 5 years of hydrate production.It is concluded that the pore pressure drop region of low-permeability reservoirs in the South China Sea is limited,and various slope angles further lead to differences in effective stress and strain of reservoirs during hydrate production,resulting in severe uneven settlement of reservoirs.

Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.

Fungi as chemical industries and genetic engineering for the production of biologically active secondary metabolites

Fungi is somewhere in between the micro and macro organisms which is a good source of producing biologically active secondary metabolites.Fungi have been used as tool for producing different types of secondary metabolites by providing different nutrients at different laboratory conditions.The fungi have been engineered for the desired secondary metabolites by using different laboratory techniques,for example,homologous and heterologous expressions.This review reported how the fungi are used as chemical industry for the production of secondary metabolites and how they are engineered in laboratory for the production of desirable metabolites:also the biosynthetic pathways of the bio-organic-molecules were reported.

China Has Successfully Conducted its First Pilot Production of Natural Gas Hydrates

Natural gas methane and hydrates are a chemical compound of water molecules formed under low temperature and high pressure. The decomposition of 1 m^3 of natural gas hydrates can release about 0.8 m^3 of water and 164 m3 of natural gas. Thus, natural gas hydrates are characterized by their high-energy density and huge resource potential. It is estimated that the world＇s total natural gas hydrates resource amount is equivalent to twice the total carbon amount of the global proven conventional fuels and can meet the human energy requirement in the future for 1000 years. They are thus the first choice to replace conventional energy of petroleum and coal.

Forecasting of China's natural gas production and its policy implications

With the vigorous promotion of energy conservation and implementation of clean energy strategies,China＇s natural gas industry has entered a rapid development phase,and natural gas is playing an increasingly important role in China＇s energy structure.This paper uses a Generalized Weng model to forecast Chinese regional natural gas production,where accuracy and reasonableness compared with other predictions are enhanced by taking remaining estimated recoverable resources as a criterion.The forecast shows that China＇s natural gas production will maintain a rapid growth with peak gas of 323 billion cubic meters a year coming in 2036;in 2020,natural gas production will surpass that of oil to become a more important source of energy.Natural gas will play an important role in optimizing China＇s energy consumption structure and will be a strategic replacement of oil.This will require that exploration and development of conventional natural gas is highly valued and its industrial development to be reasonably planned.As well,full use should be made of domestic and international markets.Initiative should also be taken in the exploration and development of unconventional and deepwater gas,which shall form a complement to the development of China＇s conventional natural gas industry.

Application of the monitoring and early warning system for internal solitary waves:Take the second natural gas hydrates production test in the South China Sea as an example

Internal solitary waves(ISWs) contain great energy and have the characteristics of emergency and concealment. To avoid their damage to offshore engineering, a new generation of monitoring and early warning system for ISWs was developed using technologies of double buoys monitoring, intelligent realtime data transmission, and automatic software identification. The system was applied to the second natural gas hydrates(NGHs) production test in the Shenhu Area, South China Sea(SCS) and successfully provided the early warning of ISWs for 173 days(from October 2019 to April 2020). The abrupt changes in the thrust force of the drilling platform under the attack of ISWs were consistent with the early warning information, proving the reliability of this system. A total of 93 ISWs were detected around the drilling platform. Most of them occurred during the spring tides in October–December 2019 and April 2020, while few of them occurred in winter. As suggested by the theoretical model, the full-depth structure of ISWs was a typical current profile of mode-1, and the velocities of wave-induced currents can reach 80 cm/s and30 cm/s, respectively, in the upper ocean and near the seabed. The ISWs may be primarily generated from the interactions between the topography and semidiurnal tides in the Luzon Strait, and then propagate westward to the drilling platform. This study could serve as an important reference for the early warning of ISWs for offshore engineering construction in the future.

Lateral bearing characteristics of subsea wellhead assembly in the hydrate trial production engineering

Conductor and suction anchor are the key equipment providing bearing capacity in the field of deep-water drilling or offshore engineering,which have the advantages of high operation efficiency and short construction period.In order to drill a horizontal well in the shallow hydrate reservoir in the deep water,the suction anchor wellhead assembly is employed to undertake the main vertical bearing capacity in the second round of hydrate trial production project,so as to reduce the conductor running depth and heighten the kick-off point position.However,the deformation law of the deep-water suction anchor wellhead assembly under the moving load of the riser is not clear,and it is necessary to understand the lateral bearing characteristics to guide the design of its structural scheme.Based on 3D solid finite element method,the solid finite element model of the suction anchor wellhead assembly is established.In the model,the seabed soil is divided into seven layers,the contact between the wellhead assembly and the soil is simulated,and the vertical load and bending moment are applied to the wellhead node to simulate the riser movement when working in the deep water.The lateral bearing stability of conventional wellhead assembly and suction anchor wellhead assembly under the influence of wellhead load is discussed.The analysis results show that the bending moment is the main factor affecting the lateral deformation of the wellhead string;the anti-bending performance from increasing the outer conductor diameter is better than that from increasing the conductor wall thickness;for the subsea wellhead,the suction anchor obviously improves the lateral bearing capacity and reduces the lateral deformation.The conduct of the suction anchor wellhead assembly still needs to be lowered to a certain depth that below the maximum disturbed depth to ensure the lateral bearing stability,Thus,a method for the minimum conductor running depth for the suction anchor wellhead assembly is developed.The field implementations show that compared with the first round of hydrate trial production project,the conductor running depth is increased by 9.42 m,and there is no risk of wellhead overturning during the trial production.The method for determining the minimum conductor running depth in this paper is feasible and will still play an important role in the subsequent hydrate exploration and development.

A Number of Major Natural Gas Production Bases Establishedby CNOOC

ItisreportedthatabundantnaturalgasresourcesexistinChina'soffshoreareasandCNOOChasalreadyestablishedanumberofmajoroffshorenaturalgasproductionbasesinSouthChinaSea,BobalSeaandEastChinaSea.Thecombinedannualproductionreaches4billioncubicmeters.Accordingt...

Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.

DNA G-Quadruplexes as Targets for Natural Product Drug Discovery

DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer therapeutics.Significantly,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and EGFR.Natural products have long been an important source of drug discovery,particularly in the fields of cancer and infectious diseases.Noteworthy progress has recently been made in the discovery of naturally occurring DNA G4-targeting drugs.Numerous DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many others.Herein,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from nature.We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.

Revealing High-Efficiency Natural Mycotoxin Antidotes in Zebrafish Model Screening Against Zearalenone-Induced Toxicity

Zearalenone(ZEA),a mycotoxin,poses a significant global hazard to human and animal health.Natural products(NPs)have shown promise for mitigating the adverse effects of ZEA owing to their diverse func-tional activities.However,the current challenge lies in the absence of an efficient strategy for systematic screening and identification of NPs that can effectively protect against ZEA-induced toxicity.This study describes a phenotype-based screening strategy for screening NP libraries and discovering more effective compounds to mitigate or counteract the adverse consequences of ZEA exposure in animals.Using this strategy,we initially identified 96 NPs and evaluated the potency and efficacy of two effective candidate compounds,fraxetin,and hydroxytyrosol,based on embryonic phenotype and locomotor activity using a scoring system and the TCMacro method.Furthermore,we performed transcriptome and proteinprotein interaction(PPI)network analyses to extract two mRNA signatures to query the Connectivity Map(CMap)database and predict NPs.The predicted NPs showed the potential to reverse the gene expression profiles associated with ZEA toxicity.Consequently,we further screened these compounds using our model,which indicated that hispidin,daphnetin,and riboflavin exhibit promising in vivo effi-cacy in zebrafish.Notably,throughout the process,fraxetin consistently stood out as the most promising NP.Biological pathway analysis and functional verification revealed that fraxetin completely reversed the toxic effects of ZEA at very low doses.This was achieved by repairing damaged cell apoptosis,modifying the cell cycle pathway,and preventing senescence induction,indicating good application potential.Overall,we demonstrated that this integration strategy can be successfully applied to effectively discover potential antidotes.