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Pore scale numerical investigation of counter-current spontaneous imbibition in multi-scaled pore networks

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Petroleum 2023年第4期9卷 558-571页

作者： Yuchen Wu xiukun wang Chaofan Zhang Chenggang Xian China University of Petroleum(Beijing) Beijing102249China

The multi-scaled pore networks of shale or tight reservoirs are considerably different from the conventional sandstone reservoirs.After hydraulic fracturing treatment,the spontaneous imbibition process plays an important role in the productivity of the horizontal wells.Applying the color-gradient model of Lattice Boltzmann Method(LBM)accelerated with parallel computing,we studied the countercurrent spontaneous imbibition process in two kinds of pore structures with different interlacing distributions of large and small pores.The effect of geometry configuration of pore arrays with different pore-scale and the capillary number Ca on the mechanism of counter-current spontaneous imbibition as well as the corresponding oil recovery factor are studied.We found that the wetting phase tends to invade the small pore array under small Ca in both types of geometry configurations of different pore arrays of four pore arrays zones.The wetting phase also tends to invade the pore array near the inlet for injecting the wetting phase no matter if it is a large pore array or small pore array except for the situation when the Ca is large to a certain value.In this situation,the small pore arrays show resistance to the wetting phase,so the wetting phase doesn't invade the small pore near the inlet,but invades the large pore preferentially.Both the geometry configurations of different pore arrays and Ca have a significant effect on the oil recovery factor.This work will help to solve the doubt about the selectivity of the multi-scaled pores of the wetting phase and the role of pores with different sizes in imbibition and oil draining in countercurrent spontaneous imbibition processes.

关键词： Countercurrent spontaneous imbibition Multi-scaled pore structures Selectivity of wetting phase to pore size Lattice Boltzmann method

Gas sorption and non-Darcy flow in shale reservoirs

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Petroleum Science 2017年第4期14卷 746-754页

作者： xiukun wang James Sheng Department of Petroleum Engineering Texas Tech UniversityPO Box 43111LubbockTX 79409USA

Gas sorption and non-Darcy flow are two important issues for shale gas reservoirs. The sorption consists of dissolution and adsorption. Dissolved gas and adsorbed gas are different. The former is dissolved in the shale matrix, while the latter is concentrated near the solid walls of pores. In this paper, the Langmuir equation is used to describe adsorption and Henry’s law is used to describe dissolution. The K coefficient in Henry’s law of 0.052 mmol/(MPa g TOC) is obtained by matching experimental data. The amount of dissolved gas increases linearly when pressure increases. Using only the Langmuir equation without considering dissolution can lead to a significant underestimation of the amount of sorbed gas in shales. For non-Darcy gas flow, the apparent permeability model for free gas is established by combining slip flow and Knudsen flow. For adsorbed gas, the surface diffusion effect is also considered in this model. The surface diffu- sion coefficient is suggested to be of the same scale as the gas self-diffusion coefficient, and the corresponding effective permeability is derived. When 1/ increases,k/ kincreases, but the relationship is not linear as the Klinkenberg effect suggests. The effect of adsorption on the gas flow is significant in nanopores (r≤2 nm). Adsorption increases apparent permeability in shales at low pressures and decreases it at high pressures.

关键词： Apparent gas permeability Shale Adsorbed gas Dissolved gas Surface diffusion

Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs

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药学学报:英文版 2023年第7期13卷 3067-3079页

作者： Zhiwen Li Zhihao Guo Xi Lu Xican Ma xiukun wang Rui Zhang Xinxin Hu Yanxiang wang Jing Pang Tianyun Fan Yonghua Liu Sheng Tang Haigen Fu Jingpu Zhang Yinghong Li Xuefu You Danqing Song Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria.Compound 33a(IMBZ18G)is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant(MDR)Gram-negative strains,with a highly druglike nature.The checkerboard assay reveals its significant synergistic effect withβ-lactamase inhibitor avibactam,and the MIC values against MDR enterobacteria were reduced up to 4—512folds.X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and Cβ-lactamases.Accordingly,preclinical studies of 33a alone and 33a-avibactam combination as potential innovative candidates are actively going on,in the treatment ofβ-lactamase-producing MDR Gram-negative bacterial infections.

关键词： Monobactam Drug-resistant gram-negative bacteria Chemoproteomic Dual mode of action Synergistic effect

New method for discretization of continuous attributes in rough set theory

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Journal of Systems Engineering and Electronics 2010年第2期21卷 250-253页

作者： Rong Cong xiukun wang Kai Li Nanhai Yang School of Electronic and Information Engineering Dalian University of Technology Dalian 116024 E R. China Education Technology Center Dalian Naval Academy Dalian 116018 P. R. China The 92538 Unit of PLA Dalian 116041 E R. China

A new method for discretization of continuous attributes is put forward to overcome the limitation of the traditional rough sets, which cannot deal with continuous attributes.The method is based on an improved algorithm to produce candidate cut points and an algorithm of reduction based on variable precision rough information entropy. With the guarantee of consistency of decision system, the method can reduce the number of cut points and im- prove efficiency of reduction. Adopting variable precision rough information entropy as measure criterion, it has a good tolerance to noise. Experiments show that the algorithm yields satisfying reduction results.

关键词： rough set discretization reduction

Polymyxin resistance caused by large-scale genomic inversion due to IS26 intramolecular translocation in Klebsiella pneumoniae

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药学学报:英文版 2023年第9期13卷 3678-3693页

作者： Haibin Li Lang Sun Han Qiao Zongti Sun Penghe wang Chunyang Xie Xinxin Hu Tongying Nie Xinyi Yang Guoqing Li Youwen Zhang xiukun wang Zhuorong Li Jiandong Jiang Congran Li Xuefu You Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100050China

Polymyxin B and polymyxin E(colistin)are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales,Acinetobacter baumannii,and Klebsiella pneumoniae.Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing.Polymyxin S2(S2)is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin.To predict the possible resistant mechanism of S2for wide clinical application,we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms.Mut-S,a resistant mutant of K.pneumoniae ATCC BAA-2146(Kpn2146)induced by S2,was analyzed by whole genome sequencing,transcriptomics,mass spectrometry and complementation experiment.Surprisingly,large-scale genomic inversion(LSGI)of approximately 1.1 Mbp in the chromosome caused by IS26mediated intramolecular transposition was found in Mut-S,which led to mgrB truncation,lipid A modification and hence S2resistance.The resistance can be complemented by plasmid carrying intact mgrB.The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146(Mut-B and Mut-E,respectively).This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K.pneumoniae.The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

关键词： Klebsiella pneumoniae Polymyxin resistance mgrB IS26 Whole genome sequencing Structural variation Inversion

Efficient generation of the mouse model with a defined point mutation through haploid cell-mediated gene editing

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Journal of Genetics and Genomics 2017年第9期44卷 461-463页

作者： Leixin Wei xiukun wang Suming Yang Wen Yuan Jinsong Li Department of Orthopaedic Surgery Changzheng Hospital The Second Military Medical University State Key Laboratory of Cell Biology Shanghai Key Laboratory of Molecular Andrology CAS Center for Excellence in Molecular Cell Science Institute of Biochemistry and Cell Biology Chinese Academy of SciencesUniversity of Chinese Academy of Sciences Department of Orthopaedic Surgery Changzheng Hospital The Second Military Medical University

Generation of mouse models carrying a defined point mutation,especially disease-related point mutations,is of considerable interest for research in biology and medicine.The standard method based on embryonic stem cell... 详细信息

关键词： ESC AG Efficient generation of the mouse model with a defined point mutation through haploid cell-mediated gene editing

Hypericin enhances β-lactam antibiotics activity by inhibiting sarA expression in methicillinresistant Staphylococcus aureus

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Acta Pharmaceutica Sinica B 2019年第6期9卷 1174-1182页

作者： Genzhu wang Liang Li xiukun wang Xue Li Youwen Zhang Jie Yu Jiandong Jiang Xuefu You Yan Q.Xiong Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center TorranceCA 90502USA Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Geffen School of Medicine at UCLA Los AngelesCA 90095USA State Key Laboratory of Bioactive Substances and Function of Natural Medicine Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Bacteremia is a life-threating syndrome often caused by methicillin-resistant Staphylococcus aureus(MRSA).Thus,there is an urgent need to develop novel approaches to successfully treat this infection.Staphylococcal accessory regulator A(SarA),a global virulence regulator,plays a critical role in pathogenesis andβ-lactam antibiotic resistance in Staphylococcus aureus.Hypericin is believed to act as an antibiotic,antidepressant,antiviral and non-specific kinase inhibitor.In the current study,we investigated the impact of hypericin onβ-lactam antibiotics susceptibility and mechanism(s)of its activity.We demonstrated that hypericin significantly decreased the minimum inhibitory concentrations ofβ-lactam antibiotics(e.g.,oxacillin,cefazolin and nafcillin),biofilm formation and fibronectin binding in MRSA strain JE2.In addition,hypericin significantly reduced sarA expression,and subsequently decreased mecAy and virulence-related regulators(e.g.,agr RNAIII)and genes(e.g.,fnbA and hla)expression in the studied MRSA strain.Importantly,the in vitro synergistic effect of hypericin withβ-lactam antibiotic(e.g.,oxacillin)translated into in vivo therapeutic outcome in a murine MRSA bacteremia model.These findings suggest that hypericin plays an important role in abrogation ofβ-lactam resistance againstMRSA through sarA inhibition,and may allow us to repurpose the use ofβ-lactam antibiotics,which are normally ineffective in the treatment of MRSA infections(e.g.,oxacillin).

关键词： Hyperiein β-Lactams MRSA Synergistic effect SarA

Discussion of liquid threshold pressure gradient

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Petroleum 2017年第2期3卷 232-236页

作者： xiukun wang James J.Sheng Texas Tech University USA Southwest Petroleum University China

Some authors believe that a minimum pressure gradient(called threshold pressure gradient(TPG))is required before a liquid starts to flow in a porous medium.In a tight or shale oil formation,this TPG phenomenon becomes more important,as it is more difficult for a fluid to flow.In this paper,experimental data on TPG published in the literature are carefully reviewed.What we found is that a very low flow velocity corresponding to a very low pressure gradient cannot be measured in the experiments.Experiments can only be done above some measurable flow velocities.If these flow velocities and their corresponding pressure gradients are plotted in an XY plot and extrapolated to zero velocity,a non-zero pressure gradient corresponds to this zero velocity.This non-zero pressure gradient is called threshold pressure gradient in the literature.However,in the regime of very low velocity and very low pressure gradient,the data gradually approach to the origin of the plot,demonstrating a non-linear relationship between the pressure gradient and the velocity.But the data do not approach to a point of zero velocity and a threshold pressure gradient.Therefore,the concept of threshold pressure gradient is a result of data misinterpretation of available experimental data.The correct interpretation is that there are two flow regimes:nonlinear flow regime(non-Darcy flow regime)when the pressure gradients are low,and linear flow regime(Darcy flow regime)when the pressure gradient is intermediate or high.The nonlinear flow regime starts from the origin point.As the pressure gradient is increased,the curve becomes a straight line demonstrating the linear flow regime.We have verified our views by first analyzing the causes of non-Darcy flow,and then systematically analyzed typical experimental data and correlations in the literature.We conclude that TPG does not exist.We also use several counter examples to support our conclusion.

关键词： Low velocity non-Darcy flow Threshold pressure gradient Shale oil reservoirs Tight oil reservoirs

In vitro and in vivo activity of D-serine in combination with β-lactam antibiotics against methicillin-resistant Staphylococcus aureus

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Acta Pharmaceutica Sinica B 2019年第3期9卷 496-504页

作者： Qing wang Yuemeng Lv Jing Pang Xue Li Xi Lu xiukun wang Xinxin Hu Tongying Nie Xinyi Yang Yan Q.Xiong Jiandong Jiang Congran Li Xuefu You Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China Los Angeles Biomedical Research Institute Harbor-UCLA Medical CenterTorranceCA90502USA David Geffen School of Medicine at UCLA Los AngelesCA90095USA State Key Laboratory of Bioactive Substances and Function of Natural Medicine Institute of Materia MedicaChinese Academy ofMedical Sciences and Peking Union Medical CollegeBeijing100050China

As D-amino acids play important roles in the physiological metabolism of bacteria,combination of D-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate in vitro and in vivo activity of D-serine alone and in combination withβ-lactams against methicillin-resistant Staphylococcus aureus(MRSA) strains, and to explore the possible sensitization mechanisms. The activity of D-serine, β-lactams alone and in combinations was evaluated both in vitro by standard MICs, time–kill curves and checkerboard assays, and in vivo by murine systemic infection model as well as neutropenic thigh infection model. An in vitro synergistic effect was demonstrated with the combination of D-serine and β-lactams against MRSA standard and clinical strains.Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared toβ-lactam alone groups. Initial mechanism study suggested possible revision of D-alanine-D-alanine residue to D-alanine-D-serine in peptidoglycan by adding of D-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, D-serine had synergistic activity in combination with β-lactams against MRSA strains both in vitro and in vivo. Considering the relatively good safety of D-serine alone or in combination with β-lactams, D-serine is worth following up as new anti-MRSA infection strategies.

关键词： MRSA D-Serine β-Lactams Combination Synergistic effect