Numerical Investigation of Combined Production of Natural Gas Hydrate and Conventional Gas

Natural gas hydrate(NGH)is generally produced and accumulated together with the underlying conventional gas.Therefore,optimizing the production technology of these two gases should be seen as a relevant way to effectively reduce the exploitation cost of the gas hydrate.In this study,three types of models accounting for the coexistence of these gases are considered.Type A considers the upper hydrate-bearing layer(HBL)adjacent to the lower conventional gas layer(CGL);with the Type B a permeable interlayer exists between the upper HBL and the lower CGL;with the type C there is an impermeable interlayer between the upper HBL and the lower CGL.The production performances associated with the above three models are calculated under different conditions,including only a depressurized HBL(only HBL DP);only a depressurized CGL(only CGL DP);and both the HBL and the CGL being depressurized(HBL+CGL DP).The results show that for Type A and Type B coexistence accumulation models,when only HBL or CGL is depressurized,the gas from the other layer will flow into the production layer due to the pressure difference between the two layers.In the coexistence accumulation model of type C,the cumulative gas production is much lower than that of Type A and Type B,regardless of whether only HBL DP,only CGL DP,or HBL+CGL DP are considered.This indicates that the impermeable interlayer restricts the cross-flow of gas between HBL and CGL.For three different coexistence accumulation models,CGL DP has the largest gas-to-water ratio.

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.

Natural Products Improve Organ Microcirculation Dysfunction Following Ischemia/Reperfusion-and Lipopolysaccharide-Induced Disturbances:Mechanistic and Therapeutic Views

Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell interactions,plasma albumin leakage,microvascular hemorrhage,and thrombosis.These disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism,the mitochondrial respiratory chain,oxidative stress,inflammatory factors,adhesion molecules,the cytoskeleton,vascular endothelial cells,caveolae,cell junctions,the vascular basement membrane,neutrophils,monocytes,and platelets.In clinical practice,aside from drugs that target abnormal vasomotor responses and platelet adhesion,there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory disturbances.Natural products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion(I/R)-and lipopolysaccharide(LPS)-induced microcirculatory disturbances.In recent years,numerous research papers on the improvement of microcirculatory function by natural products have been published in international journals.In 2008 and 2017,the first listed author of this review was invited to publish reviews in the journal of Pharmacology&Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine,respectively.This review systematically summarizes the effects,targets of action,and mechanisms of natural products regarding improving I/R-and LPSinduced microcirculatory disturbances and tissue injury.Based on this summary,scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.

Simultaneous purification of minor components in natural products using twin-column recycling chromatography with a step solvent gradient

The isolation of minor components from complex natural product matrices presents a significant challenge in the field of purification science due to their low concentrations and the presence of structurally similar compounds.This study introduces an optimized twin-column recycling chromatography method for the efficient and simultaneous purification of these elusive constituents.By introducing water at a small flowing rate between the twin columns,a step solvent gradient is created,by which the leading edge of concentration band would migrate at a slower rate than the trailing edge as it flowing from the upstream to downstream column.Hence,the band broadening is counterbalanced,resulting in an enrichment effect for those minor components in separation process.Herein,two target substances,which showed similar peak position in high performance liquid chromatography(HPLC)and did not exceed 1.8%in crude paclitaxel were selected as target compounds for separation.By using the twin-column recycling chromatography with a step solvent gradient,a successful purification was achieved in getting the two with the purity almost 100%.We suggest this method is suitable for the separation of most components in natural produces,which shows higher precision and recovery rate compared with the common lab-operated separation ways for natural products(thin-layer chromatography and prep-HPLC).

Research progress on natural products against hepatocellular carcinoma

Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable prognosis.In the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering significant interest.The integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of HCC.This review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC research.Particularly,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC activities.Natural products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.

Recent Advances of Bioactive Marine Natural Products in Drug Discovery

Marine natural products(MNPs)are valuable resources for drug development.To date,17 drugs from marine sources are in clinical use,and 33 pharmaceutical compounds are in clinical trials.Presently the success of drug development from the marine resources is higher than the industry average.It is a feasible strategy to conduct the discovery of druglead compounds based on marine chemical ecology by fully exploiting the pharmacological potential of marine chemical defense matters.In the search for bioactive MNPs,our group has constructed a biological resources library including more than 1500 strains of fungi.Focusing on the strategy of Blue Drug Library,we have discovered a series of novel MNPs with abundant biological functions.Highly efficient and scalable total synthesis of(+)-aniduquinolone A(44)and pesimquinolone I(48)have been completed,which will facilitate access to sufficient quantities of candidates for in vivo pharmacological and toxicological studies.As a nucleoprotein(NP)inhibitor,QLA(75)possesses significant anti-influenza A virus(IAV)activities both in vitro and in vivo.CHNQD-00803(76)is a potent and selective AMP-activated kinase(AMPK)activator that can effectively inhibit metabolic disorders and metabolic dysfunction-associated steatohepatitis(MASH)progression.Moreover,we identified two new candidate molecules with potent anti-hepatocellular carcinoma effects.Particularly,as a natural guanine-nucleotide exchange factors for ADP-ribosylation factor GTPases(Arf-GEFs)inhibitor prodrug,CHNQD-01255(78)is qualified to be developed as a targeted candidate anticancer drug,which may be promising to apply for cancer immunotherapy.Hence,it is evident that MNPs play an important role in drug development.

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Esophageal cancer(ESC)is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract.Although the exact pathogenesis of ESC has not been fully elucidated,excessive oxidative stress is an important characteristic that leads to the development of many cancers.Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs,which alters the growth and proliferation of ESCs and promotes their metastasis.Natural compounds,including alkaloids,terpenes,polyphenols,and xanthine compounds,can inhibit reactive oxygen species production in ESCs.These compounds reduce oxidative stress levels and subsequently inhibit the oc-currence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10,superoxide dismutase,the NF-+ACY-kappa+ADs-B/MAPK pathway,and the mammalian Nrf2/ARE target pathway.Thus,targeting tumor oxidative stress has become a key focus in anti-ESC therapy.This review discusses the potential of Natural products(NPs)for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment.The findings of this review provide a reference for drug development targeting ESCs.Nonetheless,further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

Natural product-induced oxidative stress-synergistic anti-tumor effects of chemotherapeutic agents

Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with anti-tumor effects.However,there is a lack of discussion on the synergistic anti-tumor effects of natural products in combination with chemotherapeutic drugs through reactive oxygen species.The terms“natural products”,“reactive oxygen species”,“anti-tumor”,and“chemotherapy”were used to identify the synergistic effects of natural products.We conducted a systematic literature search in PubMed and Web of Science databases for relevant research articles and reviews published in recent years.We systematically summarized the studies related to anti-tumor active ingredients in natural compounds in the field of reactive oxygen species in recent years.A total of 77 relevant literatures were included.Among them,45 literatures containing various natural products such as terpenoids,flavonoids,alkaloids,etc.exert anti-tumor effects by regulating reactive oxygen species levels,and 32 literatures regarding adjunctive role of natural products in anti-tumor therapy.In this study,we found that natural products exert anti-tumor effects by elevating reactive oxygen species levels.It provides strong theoretical support for future clinical studies.

Natural product-based treatment potential for type 2 diabetes mellitus and cardiovascular disease

BACKGROUND Type 2 diabetes(T2D)is a metabolic disease of impaired glucose utilization and a major cause of cardiovascular disease(CVD).The pathogenesis of both diseases shares common risk factors and mechanisms,and both are significant contributors to global morbidity and mortality.Supplements of natural products for T2D mellitus(T2DM)and CVD can be seen as a potential preventive and effective therapeutic strategy.AIM To critically evaluate the therapeutic potential of natural products in T2D and coronary artery disease(CAD).METHODS By using specific keywords,we strategically searched the PubMed database.Randomized controlled trials(RCTs)were searched as the primary focus that examined the effect of natural products on glycemic control,oxidative stress,and antioxidant levels.We focused on outcomes such as low blood glucose levels,adjustment on markers of oxidative stress and antioxidants.After screening fulllength papers,we included 9 RCTs in our review that met our inclusion criteria.RESULTS In the literature search on the database,we found that various natural products like plant secondary metabolites play a diverse role in the management of CAD.American ginseng,sesame oil and cocoa flavanols proved effective in lowering blood glucose levels and controlling blood pressure,which are key factors in managing T2DM and CVD.In diabetic patients Melissa officinalis effectively reduce inflammation and shows diabetes prevention.Both fish oil and flaxseed oil reduced insulin levels and inflammatory markers,suggesting benefits for both conditions.The lipid profile and endothelial function were enhanced by Nigella sativa oil and Terminalia chebula,which is significant for the management of cardiovascular risk factors in T2DM.Additionally Bilberry extract also showed promise for improving glycemic control in patients with T2DM.CONCLUSION The high level of antioxidant,anti-inflammatory,and anti-angiogenic properties found in natural products makes them promising therapeutic options for the management of CAD,with the potential benefit of lowering the risk of CAD.

SCHEMES OF GAS PRODUCTION FROM NATURAL GAS HYDRATES

Natural gas hydrates are a kind of nonpolluting and high quality energy resources for future, the reserves of which are about twice of the carbon of the current fossil energy (petroleum, natural gas and coal) on the earth. And it will be the most important energy for the 21st century. The energy balance and numerical simulation are applied to study the schemes of the natural gas hydrates production in this paper,and it is considered that both depressurization and thermal stimulation are effective methods for exploiting natural gas hydrates, and that the gas production of the thermal stimulation is higher than that of the depressurization. But thermal stimulation is non-economic because it requires large amounts of energy.Therefore the combination of the two methods is a preferable method for the current development of the natural gas hydrates. The main factors which influence the production of natural gas hydrates are: the temperature of injected water, the injection rate, the initial saturation of the hydrates and the initial temperature of the reservoir which is the most important factor.

The first offshore natural gas hydrate production test in South China Sea

Natural gas hydrates (NGH)is one of key future clean energy resources.Its industrialized development will help remit the huge demand of global natural gas,relieve the increasing pressure of the environment, and play a vital role in the green sustainable growth of human societies.Based on nearly two decades' studying on the reservoir characteristics in the South China Sea (SCS)and the knowledge of reservoir system,the China Geological Survey (CGS)conducted the first production test on an optimal target selected in Shenhu area SCS in 2017.Guided by the "three-phase control"exploitation theory which focused on formation stabilization,technologies such as formation fluid extraction,well drilling and completing, reservoir stimulating,sand controlling,environmental monitoring,monitoring and preventing of secondary formation of hydrates were applied.The test lasted for 60 days from May 10^th when starting to pump, drop pressure and ignite to well killing on July 9^th,with gas production of 3.09×10^5 m^3 in total,which is a world record with the longest continuous duration of gas production and maximal gas yield.This successful test brings a significant breakthrough on safety control of NGH production.

Preliminary results of environmental monitoring of the natural gas hydrate production test in the South China Sea

Natural gas hydrate (NGH)is considered as one of the new clean energy sources of the 21st century with the highest potential.The environmental issues of NGH production have attracted the close attention of scientists in various countries.From May 10 to July 9,2017,the first offshore NGH production test in the South China Sea (SCS)was conducted by the China Geological Survey.In addition,environmental security has also been effectively guaranteed via a comprehensive environmental monitoring system built during the NGH production test.The monitoring system considered sea-surface atmosphere methane and carbon dioxide concentrations,dissolved methane in the sea water column,and the seafloor physical oceanography and marine chemistry environment.The whole process was monitored via multiple means, in multiple layers,in all domains,and in real time.After the production test,an environmental investigation was promptly conducted to evaluate the environmental impact of the NGH production test. The monitoring results showed that the dissolved methane concentration in seawater and the near-seabed environment characteristics after the test were consistent with the background values,indicating that the NGH production test did not cause environmental problems such as methane leakage.

The second natural gas hydrate production test in the South China Sea

Clayey silt reservoirs bearing natural gas hydrates(NGH)are considered to be the hydrate-bearing reservoirs that boast the highest reserves but tend to be the most difficult to exploit.They are proved to be exploitable by the first NGH production test conducted in the South China Sea in 2017.Based on the understanding of the first production test,the China Geological Survey determined the optimal target NGH reservoirs for production test and conducted a detailed assessment,numerical and experimental simulation,and onshore testing of the reservoirs.After that,it conducted the second offshore NGH production test in 1225 m deep Shenhu Area,South China Sea(also referred to as the second production test)from October 2019 to April 2020.During the second production test,a series of technical challenges of drilling horizontal wells in shallow soft strata in deep sea were met,including wellhead stability,directional drilling of a horizontal well,reservoir stimulation and sand control,and accurate depressurization.As a result,30 days of continuous gas production was achieved,with a cumulative gas production of 86.14×104 m3.Thus,the average daily gas production is 2.87×10^4 m^3,which is 5.57 times as much as that obtained in the first production test.Therefore,both the cumulative gas production and the daily gas production were highly improved compared to the first production test.As indicated by the monitoring results of the second production test,there was no anomaly in methane content in the seafloor,seawater,and atmosphere throughout the whole production test.This successful production test further indicates that safe and effective NGH exploitation is feasible in clayey silt NGH reservoirs.The industrialization of hydrates consists of five stages in general,namely theoretical research and simulation experiments,exploratory production test,experimental production test,productive production test,and commercial production.The second production test serves as an important step from the exploratory production test to experimental production test.

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.

Experimental study on solid particle migration and production behaviors during marine natural gas hydrate dissociation by depressurization

Sand production is one of the main obstacles restricting gas extraction efficiency and safety from marine natural gas hydrate(NGH)reservoirs.Particle migration within the NGH reservoir dominates sand production behaviors,while their relationships were rarely reported,severely constrains quantitative evaluation of sand production risks.This paper reports the optical observations of solid particle migration and production from micrometer to mesoscopic scales conditioned to gravel packing during depressurization-induced NGH dissociation for the first time.Theoretical evolutionary modes of sand migration are established based on experimental observations,and its implications on field NGH are comprehensively discussed.Five particle migration regimes of local borehole failure,continuous collapse,wormhole expansion,extensive slow deformation,and pore-wall fluidization are proved to occur during depressurization.The types of particle migration regimes and their transmission modes during depressurization are predominantly determined by initial hydrate saturation.In contrast,the depressurization mainly dominates the transmission rate of the particle migration regimes.Furthermore,both the cumulative mass and the medium grain size of the produced sand decrease linearly with increasing initial methane hydrate(MH)saturation.Discontinuous gas bubble emission,expansion,and explosion during MH dissociation delay sand migration into the wellbore.At the same time,continuous water flow is a requirement for sand production during hydrate dissociation by depressurization.The experiments enlighten us that a constitutive model that can illustrate visible particle migration regimes and their transmission modes is urgently needed to bridge numerical simulation and field applications.Optimizing wellbore layout positions or special reservoir treatment shall be important for mitigating sand production tendency during NGH exploitation.

Strategies for Natural Rubber Production and Development in China

The world's natural rubber output was 12. 31 million t and the consumption reached 12. 17 million t in 2015. China's natural rubber output was 0. 85 million t and the consumption reached 4. 724 million t in 2016. Southeast Asian countries are the main natural rubber producing countries,and ITRC policy affects the natural rubber prices. During 2017-2025,the supply of natural rubber in the world is expected to be abundant to meet downstream demand. Based on natural conditions for rubber planting and production costs,China's rubber production should place emphasis on developing ClassⅠrubber production area,strengthening Class Ⅱ rubber production area and adjusting Class Ⅲ rubber production area. It is recommended to build high-output rubber plantations in Class rubber production area in Xishuangbanna; choose rubber farms with good conditions in Class Ⅱ rubber production area and build high-quality rubber production base as the dedicated production raw material base for aviation rubber; expand the Southeast Asia rubber production belt for development of natural rubber industry.

Assessment of natural resources and the policy of subsidies in grain production

Based on the analysis on the status quo of natural resources input in Brain production and on the policy of Brain subsidies, this paper puts forward a new idea - establishing grain subsidies through assessing the value of the natural resources in Brain production. The assessment of the natural resources in Brain production provides rationale and reference standard for the policy of Brain subsidies, which will promote the sustainable use of natural resources accordingly. This paper concludes： （1） it is necessary for the grain subsidies to assess the full value of natural resources, including economic value, ecological value and social value： （2） the government should give farmers direct subsidies or environment subsidies according to the economic and ecological value of natural resources in grain production, （3） the social value of natural resources can be realized by establishing the country social security system, taking the social value as the criterion for the payment for part of farmers＇ insurance.

ANTITUMOR MECHANISM OF GEM10 BY THE NATURAL KILLER ACTIVITY AND INTERLEUKIN-2 PRODUCTION

Objective To investigate th e anti-tumor effects of GeM10 by the natural killer(NK) cells activities and th e production of Interleukin-2 (IL-2) in peripheral blood mononuclear cells (PB MNCs). Methods Assay of human NK cells activities by dye reject ion assay in vitro and production of IL-2 in PBMNC by IL-2 bioassay with I L-2 dependent cell line CTLL2 and MTT colorometric method. Results GeM10 could significantly stimulate NK activities (60μg·mL -1 G eM10: 17.077±7.665, 120μg·mL -1 GeM10: 24.9±13.04; control: 7.72±4 .64, P< 0.05). GeM10 could up-regulate the production of IL-2 of PBMNCs in tumor patients(60μg·mL -1 GeM10: 2.965± 1.183; 120μg·mL -1 GeM10: 2.28±0.847; control: 1.792±0.823, P<0.05).Conclu si on The GeM10 not only can stimulate the NK activities but also increase the IL-2 production by PBMNCs in tumor patients. These findings indicate that the GeM10 may have promise as an anti-tumor drug and a biological response modi fier in clinic.