To address the persistent challenge of dynamic mismatch between wellbore lifting capacity and reservoir fluid supply,and to establish a robust optimization framework for drainage operations in high-water-cut tight san...To address the persistent challenge of dynamic mismatch between wellbore lifting capacity and reservoir fluid supply,and to establish a robust optimization framework for drainage operations in high-water-cut tight sandstone gas reservoirs,this study systematically investigates the graded optimization and dynamic adaptation of drainage gas recovery technologies.Production data from a representative tight gas field were first employed to forecast reservoir performance.The predictive reliability was rigorously validated through high-precision history matching,thereby providing a quantitatively consistent foundation for subsequent wellbore optimization.Building on this characterization,a coupled simulation framework was developed that integrates wellbore multiphase flow modeling with nodal analysis based on the Inflow Performance Relationship,IPR,and the Vertical Lift Performance,VLP.This coordinated approach enables comprehensive evaluation of process adaptability and dynamic optimization of foam-assisted drainage,mechanical pumping,and jet pumping systems under evolving water-gas ratio,WGR conditions.The results reveal that a progressively increasing water-gas ratio is the dominant factor driving the transition from chemically assisted drainage methods to mechanically enhanced lifting technologies.A distinct quantitative threshold is identified at WGR≈0.002,beyond which mechanical intervention becomes more effective and economically justified.For mechanical pumping and jet pumping systems,a parameter inversion optimization strategy constrained by the target bottomhole flowing pressure,Pwf,is proposed to ensure stable production while maintaining reservoir drawdown control.In particular,the nozzle-to-throat area ratio of the jet pump is identified as the key governing parameter influencing entrainment capacity and lifting efficiency.Moreover,a configuration characterized by small pump diameter,long stroke length,and low operating speed is demonstrated to satisfy drainage requirements while mitigating torque fluctuations,enhancing volumetric efficiency,and improving pump fillage stability.展开更多
Crimean-Congo hemorrhagic fever virus(CCHFV)is a highly pathogenic tick-borne virus that causes severe hemorrhagic fever with high mortality rates in humans.No licensed vaccines or efficacious antiviral therapies are ...Crimean-Congo hemorrhagic fever virus(CCHFV)is a highly pathogenic tick-borne virus that causes severe hemorrhagic fever with high mortality rates in humans.No licensed vaccines or efficacious antiviral therapies are currently available.Here,we identified seven heavy chain antibodies targeting CCHFV Gc,which consist of heavy-chain variable domain(VHH)fused to human IgG1 Fc region(VHHFc).These VHH-Fc antibodies exhibited neutralizing activity against both recombinant vesicular stomatitis virus(VSV)-vectored CCHFV pseudoviruses and CCHFV transcriptionand entry-competent virus-like particles(tecVLPs).Among these,N025 achieved the most potent pseudovirus neutralization,while N013 showed remarkable efficacy in tecVLP systems,with IC_(50) values of 22.7 ng/mL and 33.0 ng/mL,respectively.AlphaFold3 structural predictions revealed that all characterized VHH-Fc antibodies target epitopes within Domain Ⅱ of the Gc protein,with partial or complete overlap with the fusion loop region.Alanine scanning mutagenesis confirmed the functional significance of these epitopes,with N013 showing the highest binding energy change(ΔΔG=25.36 kcal/mol)and moderate competition with a known fusion loop-targeting antibody.Sequence conservation analysis across representative CCHFV strains from different genetic lineages demonstrated complete conservation of the N013 and N025 epitopes,suggesting potential for broad-spectrum neutralizing activity.Together,our findings provide a novel strategy for developing CCHFV therapeutics and identify promising antibody candidates that could inform future broad-spectrum antiviral development efforts.展开更多
基金supported by the Major Science and Technology Project of PetroChina Company Limited“Research on Key Technologies for Enhancing Recovery in Tight Sandstone Gas Reservoirs”,specifically under its third sub-project:“Research on Integrated Fracturing,Drainage,and Production Technology to Enhance Single-Well Production in Water-Bearing Gas Reservoirs”(Grant number:2023ZZ25YJ03).
文摘To address the persistent challenge of dynamic mismatch between wellbore lifting capacity and reservoir fluid supply,and to establish a robust optimization framework for drainage operations in high-water-cut tight sandstone gas reservoirs,this study systematically investigates the graded optimization and dynamic adaptation of drainage gas recovery technologies.Production data from a representative tight gas field were first employed to forecast reservoir performance.The predictive reliability was rigorously validated through high-precision history matching,thereby providing a quantitatively consistent foundation for subsequent wellbore optimization.Building on this characterization,a coupled simulation framework was developed that integrates wellbore multiphase flow modeling with nodal analysis based on the Inflow Performance Relationship,IPR,and the Vertical Lift Performance,VLP.This coordinated approach enables comprehensive evaluation of process adaptability and dynamic optimization of foam-assisted drainage,mechanical pumping,and jet pumping systems under evolving water-gas ratio,WGR conditions.The results reveal that a progressively increasing water-gas ratio is the dominant factor driving the transition from chemically assisted drainage methods to mechanically enhanced lifting technologies.A distinct quantitative threshold is identified at WGR≈0.002,beyond which mechanical intervention becomes more effective and economically justified.For mechanical pumping and jet pumping systems,a parameter inversion optimization strategy constrained by the target bottomhole flowing pressure,Pwf,is proposed to ensure stable production while maintaining reservoir drawdown control.In particular,the nozzle-to-throat area ratio of the jet pump is identified as the key governing parameter influencing entrainment capacity and lifting efficiency.Moreover,a configuration characterized by small pump diameter,long stroke length,and low operating speed is demonstrated to satisfy drainage requirements while mitigating torque fluctuations,enhancing volumetric efficiency,and improving pump fillage stability.
基金supported by the National Natural Science Foundation of China(grant no.82522044).
文摘Crimean-Congo hemorrhagic fever virus(CCHFV)is a highly pathogenic tick-borne virus that causes severe hemorrhagic fever with high mortality rates in humans.No licensed vaccines or efficacious antiviral therapies are currently available.Here,we identified seven heavy chain antibodies targeting CCHFV Gc,which consist of heavy-chain variable domain(VHH)fused to human IgG1 Fc region(VHHFc).These VHH-Fc antibodies exhibited neutralizing activity against both recombinant vesicular stomatitis virus(VSV)-vectored CCHFV pseudoviruses and CCHFV transcriptionand entry-competent virus-like particles(tecVLPs).Among these,N025 achieved the most potent pseudovirus neutralization,while N013 showed remarkable efficacy in tecVLP systems,with IC_(50) values of 22.7 ng/mL and 33.0 ng/mL,respectively.AlphaFold3 structural predictions revealed that all characterized VHH-Fc antibodies target epitopes within Domain Ⅱ of the Gc protein,with partial or complete overlap with the fusion loop region.Alanine scanning mutagenesis confirmed the functional significance of these epitopes,with N013 showing the highest binding energy change(ΔΔG=25.36 kcal/mol)and moderate competition with a known fusion loop-targeting antibody.Sequence conservation analysis across representative CCHFV strains from different genetic lineages demonstrated complete conservation of the N013 and N025 epitopes,suggesting potential for broad-spectrum neutralizing activity.Together,our findings provide a novel strategy for developing CCHFV therapeutics and identify promising antibody candidates that could inform future broad-spectrum antiviral development efforts.
