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1.
ACS Omega ; 9(14): 16006-16015, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38617647

RESUMO

ASP flooding is an important method to further improve oil recovery by a large margin. At present, it has entered the stage of industrial application, but there are still problems of scaling in the injection production system and high production maintenance costs. Based on the industrialized mature technology of weak alkali ASP flooding, sodium chloride is used to replace sodium carbonate, and the alkali-free three-component flooding (TC) system in the Daqing Oilfield is developed by mixing with petroleum sulfonate and partially hydrolyzed polyacrylamide. Based on the experiments of viscosity increasing, interface performance, stability, adsorption, and oil displacement effect, the differences between the alkali-free TC system and the weak alkali ASP system are compared and analyzed. The laboratory research results show that both systems are basically the same in terms of viscosity, viscoelasticity, shear resistance, interfacial activity, stability, and flowability. Due to the lack of alkaline water, the adsorption, emulsification, and oil displacement performance of the alkali-free TC system is slightly lower than that of the weak alkali ASP system. The recovery factor of core flooding can be increased by 27.31% over water flooding, which is 2.56 percentage points lower than that of the weak alkali ASP system. On the premise of the same 1% EOR effect, the agent cost of the alkali-free system is 17.02% lower than that of the alkali ASP system. This article innovatively verifies the feasibility of using NaCl instead of Na2CO3 and explains the mechanism of significantly improving oil recovery in composite systems under alkali-free conditions from the ion level. However, the emulsification effect of the alkali-free TC system is relatively weak. The next step of research would be to consider adding an E-surfactant to enhance the emulsification performance of the composite system. By improving the system composition, technical references are provided for the efficient development of other terrestrial sandstone oilfields.

2.
Nanoscale ; 16(17): 8434-8446, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38592819

RESUMO

Combination therapy has proven effective in counteracting tumor multidrug resistance (MDR). However, the pharmacokinetic differences among various drugs and inherent water insolubility for most small molecule agents greatly hinder their synergistic effects, which makes the delivery of drugs for combination therapy in vivo a key problem. Herein, we propose a protonated strategy to transform a water-insoluble small molecule drug-inhibitor conjugate into an amphiphilic one, which then self-assembles into nanoparticles for co-delivery in vivo to overcome tumor MDR. Specifically, paclitaxel (PTX) is first coupled with a third-generation P-glycoprotein (P-gp) inhibitor zosuquidar (Zos) through a glutathione (GSH)-responsive disulfide bond to produce a hydrophobic drug-inhibitor conjugate (PTX-ss-Zos). Subsequently treated with hydrochloric acid ethanol solution (HCl/EtOH), PTX-ss-Zos is transformed into the amphiphilic protonated precursor and then forms nanoparticles (PTX-ss-Zos@HCl NPs) in water by molecular self-assembly. PTX-ss-Zos@HCl NPs can be administered intravenously and accumulated specifically at tumor sites. Once internalized by cancer cells, PTX-ss-Zos@HCl NPs can be degraded under the overexpressed GSH to release PTX and Zos simultaneously, which synergistically reverse tumor MDR and inhibit tumor growth. This offers a promising strategy to develop small molecule self-assembled nanoagents to reverse tumor MDR in combination therapy.


Assuntos
Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas , Paclitaxel , Humanos , Paclitaxel/química , Paclitaxel/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Camundongos , Nanopartículas/química , Linhagem Celular Tumoral , Camundongos Nus , Prótons , Camundongos Endogâmicos BALB C , Antineoplásicos/química , Antineoplásicos/farmacologia , Portadores de Fármacos/química , Feminino , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo
3.
ACS Appl Mater Interfaces ; 15(50): 58067-58078, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38056905

RESUMO

Recently, cell membrane camouflaged nanoparticles (NPs) endowed with natural cellular functions have been extensively studied in various biomedical fields. However, there are few reports about such biomimetic NPs used to codeliver chemodrug and genes for synergistic cancer treatment up to now. Herein, we first prepare chemodrug-gene nanoparticles (Mito-Her2 NPs) by the electrostatic interaction coself-assembly of mitoxantrone hydrochloride (Mito) and human epidermal growth factor receptor-2 antisense oligonucleotide (Her2 ASO). Then, Mito-Her2 NPs are coated by a hybrid membrane (RSHM), consisting of the red blood cell membrane (RBCM) and the SKOV3 ovarian cancer cell membrane (SCM), to produce biomimetic chemodrug-gene nanoparticles (Mito-Her2@RSHM NPs) for combination therapy of ovarian cancer. Mito-Her2@RSHM NPs integrate the advantages of RBCM (e.g., good immune evasion capability and long circulation lifetime in the blood) and SCM (e.g., highly specific cognate recognition) together and improve the anticancer efficacy of Mito-Her2 NPs. The results show that Mito-Her2@RSHM NPs can be devoured by SKOV3 ovarian cancer cells and effectively degraded to release Her2 ASOs and Mito simultaneously. Her2 ASOs can inhibit the expression of endogenous Her2 genes and recover cancer cells' sensitivity to Mito, which ultimately led to a high apoptosis rate of 75.7% in vitro. Mito-Her2@RSHM NPs also show a high tumor suppression rate of 83.33 ± 4.16% in vivo without significant damage to normal tissues. In summary, Mito-Her2@RSHM NPs would be expected as a versatile and safe nanodrug delivery platform with high efficiency for chemo-gene combined cancer treatment.


Assuntos
Nanopartículas , Neoplasias Ovarianas , Humanos , Feminino , Linhagem Celular Tumoral , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Membrana Eritrocítica/metabolismo , Apoptose , Mitomicina , Nanopartículas/uso terapêutico
4.
ACS Omega ; 8(43): 40051-40062, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37929121

RESUMO

So far, alkali/surfactant/polymer flooding is widely used in oilfields to improve recovery. However, the introduction of alkali to the ternary composite leads to substantial damage formation, accelerates the scaling and corrosion loss in all aspects of surface injection and recovery, and consequently increases the cost of oil recovery in the ternary composite drive field. Therefore, environmentally friendly means are in urgent demand. Alternatively, a new non-alkali ternary drive system with salt instead of alkali has been developed based on the basis of ternary composite drive in the Daqing oilfield. In this experiment, a mathematical model of oil repelling by a salt-substituted alkali-free ternary emulsion system is formed, followed by the verification of the wet-lab experiments. The results show that the alkali-free ternary emulsion system can have a synergistic effect of complex salt and petroleum sulfonate surfactant and represents a wide range of ultralow interfacial tensions and good oil-repelling performances. The chromatographic separation occurs in the transmission process due to the adsorption of porous media, and the lower the permeability and the lower the injection rate, the higher the chromatographic separation degree. The use of multistage plug injection can narrow the difference of flow rate between high and low permeability layers and improve the recovery rate to 61.59%. Herein, the results provide theoretical guidance for the application of an alkali-free ternary emulsification system.

5.
ACS Omega ; 8(42): 38926-38932, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37901524

RESUMO

Low permeability reservoirs are characterized by low permeability, small pore throat, strong heterogeneity, and poor injection-production ability. High shale content of the reservoir, strong pressure sensitivity, micropore undersaturation, and significant water-lock effect in water injection development lead to increased fluid seepage resistance. There is an urgent need to adopt physical and chemical methods to supplement energy and improve infiltration efficiency, thereby forming effective methods for increasing the production and efficiency. Aiming at the characteristics of ultralow permeability reservoirs, in this paper, a green and environmental friendly biobased profile control and displacement agent (Bio Nano30) has been developed using noncovalent supramolecular interaction. Physical simulation experiments illustrate the profile control and displacement mechanism of Bio-Nano30. Laboratory experiments and field applications show that good results have been achieved in oil well plugging removal, water well pressure reduction and injection increase, and well group profile control and oil displacement. This research has good application prospects in low permeability heterogeneous reservoirs.

6.
Polymers (Basel) ; 15(3)2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36771910

RESUMO

With the acceleration in oilfield developments, reservoir advantage channels have been gradually developed. This has led to ineffective circulation in the oilfield injection system and a significant decrease in production. The profile control and displacement technology of low-permeability and heterogeneous reservoirs are in urgent need of updating. In this paper, an intelligent profile control and displacement agent is proposed. The controlled release mechanism and profile control and displacement mechanism is clarified by physical simulation experiments. The profile control agent is a nanocapsule with environmental response and controlled release. The structure of the capsule is a core-shell structure, which is composed of an amphiphilic copolymer AP-g-PNIPAAM and Janus functional particles. The surface chemical stability of the micro/nanocapsule is analyzed by a potentiometric method. The study shows that a temperature at 45 °C causes a potential change in the micro/nanocapsule, indicating that the micro/nanocapsule has a slow release at this temperature. When the temperature is in the range of 40 to 45 °C, the absorbance greatly increases; therefore, it is considered that the capsule wall LCST is about 45 °C. Heating causes the surface contraction of the capsule wall to intensify, the micropores in the capsule wall to increase, the release amount to increase and the release rate per unit time to increase. The release time increases proportionally with the increase in capsule wall thickness. When the release time is the same, an alkaline or acidic environment can improve the release rate of the nanocapsule. The effect of profile control and flooding is evaluated through different differential core models. The research shows that the controlled release micro/nanocapsule has a good environmental response and the internal components can be effectively controlled by adjusting the temperature or pH value. This research has shown that the nanocapsules have good application prospects in low-permeability heterogeneous reservoirs.

7.
Plants (Basel) ; 11(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36501284

RESUMO

Identification and accurate mapping of new resistance genes are essential for gene pyramiding in wheat breeding. The YrJ22 gene is a dominant stripe-rust-resistance gene located at the distal end of chromosome 2AL, which was identified in a leading Chinese-wheat variety, Jimai 22, showing high resistance to CYR32, a prevalent race of Puccinia striiformis tritici (Pst) in China. In the current study, 15 F1 and 2273 F2 plants derived from the cross of Jimai 22/Avocet S were used for the fine-mapping of YrJ22. The RNA-Seq of resistant and susceptible bulks of F2 plants (designated BSR-Seq) identified 10 single-nucleotide polymorphisms (SNP) in a 12.09 Mb physical interval on chromosome 2AL. A total of 1022 EMS-induced M3 lines of Jimai 22 were screened, to identify susceptible mutants for MutMap analysis. Four CAPS markers were developed from SNPs identified using BSR-Seq and MutMap. A linkage map for YrJ22 was constructed with 11 CAPS/STS and three SSR markers. YrJ22 was located at a 0.9 cM genetic interval flanked by markers H736 and H400, corresponding to a 340.46 kb physical region (768.7-769.0 Mb), including 13 high-confidence genes based on the Chinese Spring reference genome. TraesCS2A01G573200 is a potential candidate-gene, according to linkage and quantitative real-time PCR (qPCR) analyses. The CAPS marker H732 designed from an SNP in TraesCS2A01G573200 co-segregated with YrJ22. These results provide a useful stripe-rust-resistance gene and molecular markers for marker-assisted selection in wheat breeding and for further cloning of the gene.

8.
Theor Appl Genet ; 135(10): 3485-3496, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35986759

RESUMO

KEY MESSAGE: A stripe rust resistance gene YrZM175 in Chinese wheat cultivar Zhongmai 175 was mapped to a genomic interval of 636.4 kb on chromosome arm 2AL, and a candidate gene was predicted. Stripe rust, caused by Puccinia striiformis f. sp. tritici (PST), is a worldwide wheat disease that causes large losses in production. Fine mapping and cloning of resistance genes are important for accurate marker-assisted breeding. Here, we report the fine mapping and candidate gene analysis of stripe rust resistance gene YrZM175 in a Chinese wheat cultivar Zhongmai 175. Fifteen F1, 7,325 F2 plants and 117 F2:3 lines derived from cross Avocet S/Zhongmai 175 were inoculated with PST race CYR32 at the seedling stage in a greenhouse, and F2:3 lines were also evaluated for stripe rust reaction in the field using mixed PST races. Bulked segregant RNA-seq (BSR-seq) analyses revealed 13 SNPs in the region 762.50-768.52 Mb on chromosome arm 2AL. By genome mining, we identified SNPs and InDels between the parents and contrasting bulks and mapped YrZM175 to a 0.72-cM, 636.4-kb interval spanned by YrZM175-InD1 and YrZM175-InD2 (763,452,916-764,089,317 bp) including two putative disease resistance genes based on IWGSC RefSeq v1.0. Collinearity analysis indicated similar target genomic intervals in Chinese Spring, Aegilops tauschii (2D: 647.7-650.5 Mb), Triticum urartu (2A: 750.7-752.3 Mb), Triticum dicoccoides (2A: 771.0-774.5 Mb), Triticum turgidum (2B: 784.7-788.2 Mb), and Triticum aestivum cv. Aikang 58 (2A: 776.3-778.9 Mb) and Jagger (2A: 789.3-791.7 Mb). Through collinearity analysis, sequence alignments of resistant and susceptible parents and gene expression level analysis, we predicted TRITD2Bv1G264480 from Triticum turgidum to be a candidate gene for map-based cloning of YrZM175. A gene-specific marker for TRITD2Bv1G264480 co-segregated with the resistance gene. Molecular marker analysis and stripe rust response data revealed that YrZM175 was different from genes Yr1, Yr17, Yr32, and YrJ22 located on chromosome 2A. Fine mapping of YrZM175 lays a solid foundation for functional gene analysis and marker-assisted selection for improved stripe rust resistance in wheat.


Assuntos
Basidiomycota , Triticum , Basidiomycota/fisiologia , Pão , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Resistência à Doença/genética , Marcadores Genéticos , Melhoramento Vegetal , Doenças das Plantas/genética , Triticum/genética
9.
ACS Omega ; 7(27): 23107-23114, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35847275

RESUMO

According to the research status of low-permeability reservoir development, in order to find an intelligent and efficient displacement method, a Janus smart nanocapsule (embedding nanomaterials with surfactant function into the polymer) is developed in this paper. There are two kinds of phase fluids in the migration of porous media, the initial Janus intelligent microcapsule slow-release liquid (dissolved and undissolved AP-g-PNIPAAM and Janus functional particle ternary dispersion) and the later AP-g-PNIPAAM and Janus functional particle binary dispersion. Comprehensively, using the indoor oil displacement experiment, the seepage characteristics of the Janus smart nanocapsule (JSNC) in porous media are studied, and their macro and micro oil displacement mechanisms are revealed. Research shows that Janus intelligent microcapsules have good mobility control ability in low-permeability heterogeneous reservoirs. The displacement performance of stepped differential pressure shows that the displacement medium can expand the swept volume. The research results presented can show that the JSNC oil displacement system has great application potential for the development of low-permeability reservoirs.

10.
ACS Omega ; 7(1): 55-63, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35036678

RESUMO

With the development of the petroleum industry, oil pollution has become widespread. It is harmful to the digestive, immune, reproductive, and nervous systems of fishes, wild animals, and humans, causing severe threats to ecological safety and human health. Gordonia has increasingly attracted attention in the treatment of alkane pollution for its outstanding performance against hydrophobic refractory substances. However, the lack of knowledge about alkane uptake and degradation restricts the application of gordonia. In this paper, we studied the strain lys1-3 of Gordonia sihwaniensis isolated from coal chemical wastewater, which showed good alkane degradation performance by lys1-3. It is found that stimulated by an alkane, lys1-3 secreted biosurfactants, which emulsified large alkane particles to smaller particles. By active transport, unmodified alkane was transferred into cells and produced a large amount of acid, which was secreted out of the cells.

11.
ACS Omega ; 6(25): 16507-16516, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34235322

RESUMO

Component transportation is one of the main mechanisms for numerical simulation in microbial oil recovery. However, the research on the component transportation considering the inhibition of metabolites is very limited. A mathematical model of oil displacement in a microorganism system including microbial growth and metabolism equation, component transport equation, and porous media physical property variation equation was established in this paper. The equation was discretized and solved by implicit pressure and explicit saturation. The MATLAB simulation results showed that the chromatographic separation between microorganisms and nutrients happened because of the adsorption of porous media and the activity of microorganisms during the transportation, and the separation degree of the chromatography became higher as the permeability became lower and the injection speed became slower. The multislug alternative injection mode could reduce the degree of chromatographic separation, and the recovery rate can be increased to 50.82%. The results of this study could provide theoretical guidance for the popularization and application of microbial enhanced oil recovery (MEOR).

12.
Theor Appl Genet ; 133(10): 2897-2914, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32594265

RESUMO

KEY MESSAGE: GWAS identified 36 potentially new loci for wheat stem water-soluble carbohydrate (WSC) contents and 13 pleiotropic loci affecting WSC and thousand-kernel weight. Five KASP markers were developed and validated. Water-soluble carbohydrates (WSC) reserved in stems contribute significantly to grain yield (GY) in wheat. However, knowledge of the genetic architecture underlying stem WSC content (SWSCC) is limited. In the present study, 166 diverse wheat accessions from the Yellow and Huai Valleys Winter Wheat Zone of China and five other countries were grown in four well-watered environments. SWSCC at 10 days post-anthesis (10DPA), 20DPA and 30DPA, referred as WSC10, WSC20 and WSC30, respectively, and thousand-kernel weight (TKW) were assessed. Correlation analysis showed that TKW was significantly and positively correlated with WSC10 and WSC20. Genome-wide association study was performed on SWSCC and TKW with 373,106 markers from the wheat 660 K and 90 K SNP arrays. Totally, 62 stable loci were detected for SWSCC, with 36, 24 and 19 loci for WSC10, WSC20 and WSC30, respectively; among these, 36 are potentially new, 16 affected SWSCC at two or three time-points, and 13 showed pleiotropic effects on both SWSCC and TKW. Linear regression showed clear cumulative effects of favorable alleles for increasing SWSCC and TKW. Genetic gain analyses indicated that pyramiding favorable alleles of SWSCC had simultaneously improved TKW. Kompetitive allele-specific PCR markers for five pleiotropic loci associated with both SWSCC and TKW were developed and validated. This study provided a genome-wide landscape of the genetic architecture of SWSCC, gave a perspective for understanding the relationship between WSC and GY and explored the theoretical basis for co-improvement of WSC and GY. It also provided valuable loci and markers for future breeding.


Assuntos
Carboidratos/análise , Triticum/genética , Alelos , Frequência do Gene , Estudos de Associação Genética , Marcadores Genéticos , Pleiotropia Genética , Genótipo , Desequilíbrio de Ligação , Fenótipo , Mapeamento Físico do Cromossomo , Caules de Planta/química , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Água
13.
Front Chem ; 8: 154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32195226

RESUMO

Based on the development status of low permeability reservoirs, an intelligent nano-flooding agent is needed to improve the displacement efficiency of reservoirs. Janus particles have the characteristics of small size and strong interfacial activity, and the solid surfactant of Janus particles has attracted more and more attention of petroleum researchers. Janus smart nanosheets were developed by Pickering emulsion preparation. Controllable assemblies of Janus smart nanosheets were formed by adjusting the preparation ratio. The structure and properties of smart nanosheets were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy and interfacial tensiometer. The nanosheets have hydrophilic and hydrophilic properties. The particle size of silica nanoparticle is 10 nm. After surface modification and high shear stress treatment, nanosheet was formed. The thickness of nanosheet dispersed in aqueous solution was 30.2 nm. Experimental results show that at a given temperature, the Janus nanosheet system with low concentration can achieve ultra-low interfacial tension of 10-4 mN /m, and the nanosheets have good emulsifying ability. The results provide basic insights into the bio-assembly behavior and emulsifying properties of Janus smart nanosheets, and further prove their potential for enhancing oil recovery.

14.
Materials (Basel) ; 12(7)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30987019

RESUMO

Micro-/nanomotors colloidal particles have attracted increasing interest as composite surfactants, owing to the combined advantages of both Janus solid surfactants and micro-/nanomotors. Here we put micro-/nanomotors colloidal particles into hollow polymeric micro-encapsulates. An intelligent polymeric nanocapsule was prepared for enhanced oil recovery by the self-assembly method. The particle size range of the polymeric capsule can be controlled between 20 to 1000 nm by adjusting the cross-linking thickness of the capsule's outer membrane. The average particle size of polymeric capsules prepared in the study was 300 nm. The structure and properties of the Intelligent polymeric nanocapsule was characterized by a wide range of technics such as Fourier transform infrared spectroscopy, scanning electron microscopy by laser diffraction, fluorescence microscopy, pendant drop tensiometer, laser particle size instrument, and interface tension analyzer. It was found that the intelligent polymeric nanocapsule exhibited significant interfacial activity at the oil-water interface. When the Janus particles' concentration reached saturation concentration, the adsorption of the amphiphilic nanoparticles at the interface was saturated, and the equilibrium surface tension dropped to around 31 mN/m. When the particles' concentration reached a critical concentration of aggregation, the Gibbs stability criterion was fulfilled. The intelligent polymeric nanocapsule system has a better plugging and enhanced oil recovery capacity. The results obtained provide fundamental insights into the understanding of the assembly behavior and emulsifying properties of the intelligent polymeric nanocapsule, and further demonstrate the future potential of the intelligent polymeric nanocapsule used as colloid surfactants for enhanced oil recovery applications.

15.
Arterioscler Thromb Vasc Biol ; 38(8): 1837-1844, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29976768

RESUMO

Objective- Genome-wide association studies have revealed a robust association between genetic variation on chromosome 15q26.1 and coronary artery disease (CAD) susceptibility; however, the underlying biological mechanism is still unknown. The lead CAD-associated genetic variant (rs17514846) at this locus resides in the FURIN gene. In advanced atherosclerotic plaques, furin is expressed primarily in macrophages. We investigated whether this CAD-associated variant alters FURIN expression and whether furin affects monocyte/macrophage behavior. Approach and Results- A quantitative reverse transcription polymerase chain reaction analysis showed that leukocytes from individuals carrying the CAD risk allele (A) of rs17514846 had increased FURIN expression. A chromatin immunoprecipitation assay revealed higher RNA polymerase II occupancy in the FURIN gene in mononuclear cells of individuals carrying this allele. A reporter gene assay in transiently transfected monocytes/macrophages indicated that the CAD risk allele had higher transcriptional activity than the nonrisk allele (C). An analysis of isogenic monocyte cell lines created by CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing showed that isogenic cells with the A/A genotype for rs17514846 had higher FURIN expression levels than the isogenic cells with the C/C genotype. An electrophoretic mobility shift assay exhibited preferential binding of a nuclear protein to the risk allele. Studies of monocytes/macrophages with lentivirus-mediated furin overexpression or shRNA (short hairpin RNA)-induced furin knockdown showed that furin overexpression promoted monocyte/macrophage migration, increased proliferation, and reduced apoptosis whereas furin knockdown had the opposite effects. Conclusions- Our study shows that the CAD-associated genetic variant increases FURIN expression and that furin promotes monocyte/macrophage migration and proliferation while inhibiting apoptosis, providing a biological mechanism for the association between variation at the chromosome 15q26.1 locus and CAD risk.


Assuntos
Doença da Artéria Coronariana/enzimologia , Doença da Artéria Coronariana/genética , Furina/genética , Furina/metabolismo , Ativação de Macrófagos , Macrófagos/enzimologia , Polimorfismo de Nucleotídeo Único , Animais , Apoptose , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Doença da Artéria Coronariana/diagnóstico por imagem , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Macrófagos/patologia , Camundongos , Fenótipo , Células RAW 264.7 , Transdução de Sinais , Células THP-1
16.
Sci Rep ; 6: 38025, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27905492

RESUMO

Continuous flow ventricular assist devices (cfVADs) provide a life-saving therapy for severe heart failure. However, in recent years, the incidence of device-related thrombosis (resulting in stroke, device-exchange surgery or premature death) has been increasing dramatically, which has alarmed both the medical community and the FDA. The objective of this study was to gain improved understanding of the initiation and progression of thrombosis in one of the most commonly used cfVADs, the Thoratec HeartMate II. A computational fluid dynamics simulation (CFD) was performed using our recently updated mathematical model of thrombosis. The patterns of deposition predicted by simulation agreed well with clinical observations. Furthermore, thrombus accumulation was found to increase with decreased flow rate, and can be completely suppressed by the application of anticoagulants and/or improvement of surface chemistry. To our knowledge, this is the first simulation to explicitly model the processes of platelet deposition and thrombus growth in a continuous flow blood pump and thereby replicate patterns of deposition observed clinically. The use of this simulation tool over a range of hemodynamic, hematological, and anticoagulation conditions could assist physicians to personalize clinical management to mitigate the risk of thrombosis. It may also contribute to the design of future VADs that are less thrombogenic.


Assuntos
Anticoagulantes/uso terapêutico , Coração Auxiliar/efeitos adversos , Trombose/tratamento farmacológico , Trombose/etiologia , Simulação por Computador , Feminino , Hemodinâmica , Humanos , Hidrodinâmica , Masculino , Fluxo Pulsátil , Propriedades de Superfície
17.
PLoS Genet ; 12(7): e1006127, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27389912

RESUMO

Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk.


Assuntos
Colágeno Tipo IV/genética , Doença das Coronárias/genética , Estudo de Associação Genômica Ampla , Infarto do Miocárdio/genética , Alelos , Doença das Coronárias/patologia , Feminino , Genótipo , Humanos , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Mutação , Infarto do Miocárdio/patologia , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologia , Polimorfismo de Nucleotídeo Único
18.
Environ Sci Pollut Res Int ; 23(6): 5288-95, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26564183

RESUMO

China's Sloping Land Conversion Program (SLCP) was designed to restore perennial plant cover on sloping land in western China, in part to protect the Three Gorges Reservoir (TGR). In this study, we examined use of white mulberry (Morus alba L.) in the SLCP to protect water quality and conserve soil. We established nine runoff monitoring plots divided among three categories (vegetable farming, fallow control, and mulberry plantation) on a bank of the Liangtan River situated at the western margin of the TGR. The land had been used previously by farmers for growing vegetables. We found that soil loss and surface water runoff were lowest in the mulberry plots and highest in the vegetable plots. We used inductively coupled plasma atomic emission spectroscopy (ICP-AES) to assess the concentration of selected heavy metal pollution indicators (Zn, Hg, As, Ni, Pb, Cr, Cd, and Cu) in the monitoring plot soils at the beginning of the experiment in May 2009. The heavy metals were assessed again at the end of the experiment in October 2012, and we found that the concentrations of these pollutants had been reduced in all fallow and mulberry plots, and to the greatest extent in the mulberry plots. We found that levels of Hg, Pb, and Cu increased in the vegetable plots. For these reasons, we conclude that riparian mulberry plantations are useful for reducing rapid runoff of storm water, conserving soil, and sequestering heavy metal pollutants in the TGR region.


Assuntos
Monitoramento Ambiental/métodos , Metais Pesados/análise , Morus , Poluentes do Solo/análise , Morus/química , Morus/metabolismo , Solo/química , Qualidade da Água
19.
Artif Organs ; 34(5): 402-11, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19832736

RESUMO

An important challenge facing the design of turbodynamic ventricular assist devices (VADs) intended for long-term support is the optimization of the flow path geometry to maximize hydraulic performance while minimizing shear-stress-induced hemolysis and thrombosis. For unshrouded centrifugal, mixed-flow and axial-flow blood pumps, the complex flow patterns within the blade tip clearance between the lengthwise upper surface of the rotating impeller blades and the stationary pump housing have a dramatic effect on both the hydrodynamic performance and the blood damage production. Detailed computational fluid dynamics (CFD) analyses were performed in this study to investigate such flow behavior in blade tip clearance region for a centrifugal blood pump representing a scaled-up version of a prototype pediatric VAD. Nominal flow conditions were analyzed at a flow rate of 2.5 L/min and rotor speed of 3000 rpm with three blade tip clearances of 50, 100, and 200 microm. CFD simulations predicted a decrease in the averaged tip leakage flow rate and an increase in pump head and axial thrust with decreasing blade tip clearances from 200 to 50 microm. The predicted hemolysis, however, exhibited a unimodal relationship, having a minimum at 100 microm compared to 50 microm and 200 microm. Experimental data corroborate these predictions. Detailed flow patterns observed in this study revealed interesting fluid dynamic features associated with the blade tip clearances, such as the generation and dissipation of tip leakage vortex and its interaction with the primary flow in the blade-blade passages. Quantitative calculations suggested the existence of an optimal blade tip clearance by which hydraulic efficiency can be maximized and hemolysis minimized.


Assuntos
Coração Auxiliar , Hemodinâmica , Criança , Simulação por Computador , Desenho de Equipamento , Hemólise , Humanos , Modelos Biológicos , Estresse Mecânico
20.
Artif Organs ; 32(2): 127-35, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18005272

RESUMO

This article describes a design process for a new pediatric ventricular assist device, the PediaFlow. The pump is embodied in a magnetically levitated turbodynamic design that was developed explicitly based on the requirements for chronic support of infants and small children. The procedure entailed the consideration of multiple pump topologies, from which an axial mixed-flow configuration was chosen for further development. The magnetic design includes permanent-magnet (PM) passive bearings for radial support of the rotor, an actively controlled thrust actuator for axial support, and a brushless direct current (DC) motor for rotation. These components are closely coupled both geometrically and magnetically, and were therefore optimized in parallel, using electromagnetic, rotordynamic models and fluid models, and in consideration of hydrodynamic requirements. Multiple design objectives were considered, including efficiency, size, and margin between critical speeds to operating speed. The former depends upon the radial and yaw stiffnesses of the PM bearings. Analytical expressions for the stiffnesses were derived and verified through finite element analysis (FEA). A toroidally wound motor was designed for high efficiency and minimal additional negative radial stiffness. The design process relies heavily on optimization at the component level and system level. The results of this preliminary design optimization yielded a pump design with an overall stability margin of 15%, based on a pressure rise of 100 mm Hg at 0.5 lpm running at 16,000 rpm.


Assuntos
Desenho de Equipamento , Coração Auxiliar , Magnetismo , Engenharia Biomédica , Pré-Escolar , Análise de Elementos Finitos , Humanos , Lactente , Recém-Nascido , Modelos Biológicos
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