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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 and β-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 on β-lactam antibiotics susceptibility and mechanism(s) of its activity. We demonstrated that hypericin significantly decreased the minimum inhibitory concentrations of β-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 mecA, 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 with β-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 of β-lactam resistance against MRSA through sarA inhibition, and may allow us to repurpose the use of β-lactam antibiotics, which are normally ineffective in the treatment of MRSA infections (e.g., oxacillin).

BackgroundAntibiotic-resistant H. pylori was increasingly found in infected individuals, which resulted in treatment failure and required alternative therapeutic strategies. Daphnetin, a coumarin-derivative compound, has multiple pharmacological activities.MethodsThe mechanism of daphnetin on H. pylori was investigated focusing on its effect on cell morphologies, transcription of genes related to virulence, adhesion, and cytotoxicity to human gastric epithelial (GES-1) cell line.ResultsDaphnetin showed good activities against multidrug resistant (MDR) H. pylori clinical isolates, with minimal inhibitory concentration (MIC) values ranging from 25 to 100 μg/mL. In addition, daphnetin exposure resulted in H. pylori morphological changes. Moreover, daphnetin caused increased translocation of phosphatidylserine (PS), DNA damage, and recA expression, and RecA protein production vs. control group. Of great importance, daphnetin significantly decreased H. pylori adhesion to GES-1 cell line vs. control group, which may be related to the reduced expression of colonization related genes (e.g., babA and ureI).ConclusionsThese results suggested that daphnetin has good activity against MDR H. pylori. The mechanism(s) of daphnetin against H. pylori were related to change of membrane structure, increase of DNA damage and PS translocation, and decrease of H. pylori attachment to GES-1 cells.

The characteristics of karst reservoirs are extremely varied and anisotropic, exhibiting notable differences in porosity, permeability, and corresponding fluid flow pathways. Fractured karst petroleum reservoirs, such as distinct caverns and fractures, are an example of a typical discrete media type. The traditional reservoir modeling approach and discrete fracture-like local refinement models are unsuitable for field application of fractured karst oil reservoirs due to the needs of high fidelity geological description and huge computing efforts. Based directly on the spatial characteristics of seismic surveys, a numerical simulation model in three dimensions, akin to a node-like network, is presented here for cracked karst oil reserves. First, the watershed image processing technique and the automatic connection identification procedure are used to extract the three-dimensional node-network model. After that, automatic differentiation is used to build the numerical finite volume scheme, and the proper gradient-based adjoint approach is used to conduct the related historical matching rapidly. After validation by a synthetic model in a commercial simulator, this proposed three-dimensional network numerical model is used for a field reservoir block of deep formation in the Tarim basin to demonstrate its computational efficiency and viability for enormously comparable karst oil reservoirs. [ABSTRACT FROM AUTHOR]

Filling through-glass vias (TGVs) with liquid remains a significant challenge in IC packaging technology. This study presents an acoustic-streaming method to modulate the wetting behavior as well as the interfacial dynamics to fill the TGVs. We categorize the incomplete filling into three typical patterns: (a) neck wetting, (b) head and end wetting, and (c) bubble wrapping. Experimental results show that the ultrasonic driving at 522.5 kHz / 160 V can effectively achieve ideal filling of these patterns in TGVs (aspect ratio of 1 : 2 / 1 : 3). The filling processes are elucidated from a new perspective: the liquid flow induced by acoustic streaming regulates the moving of contact line to complete wetting on sidewalls, while the acoustic wave impacts the gas–liquid interface to cause oscillations for pushing bubbles out. A Lattice Boltzmann model is constructed to reveal the mechanism. This method offers a viable and promising solution to promote liquid filling of TGVs. [ABSTRACT FROM AUTHOR]

Foam flooding is an effective oil displacement technique to improve fluid sweep efficiency and increase oil recovery. The objective of this paper is to investigate the applicability of ultra-low IFT foam flooding for low permeability oil recovery under the conditions of WX reservoir block in Tuha oilfield (84°C, 86,072 mg/L). A modified amphoteric hydroxy sulfobetaine surfactant (Cn-HSB) was formulated as a foaming agent based on the principle of compatibility with crude oil that could achieve the ultra-low interfacial tension (IFT) and strong foamability simultaneously. This is shown to reduce the oil/water dynamic IFT (DIFT) to an ultra-low value of the order of 10-5 mN/m (0.10wt%), as well as produce a foam volume and half-life of 448 mL and 2567 s, respectively. In addition, results of IFT and foam quality tests indicate that the modified Cn-HSB has good thermal stability and excellent salinity-resistance. Moreover, the ultra-low IFT foam flooding has an ideal injectivity and oil displacement efficiency in low permeability porous media that can mobilize the trapped oil in k = 1.50 χ 10-3μιτι2 with a threshold pressure gradient of 0.115 MPa/m. This improves oil displacement efficiency about 15%OOIP. Fundamental knowledge gained from this research gives insight into the application of ultra-low IFT foam flooding in low-permeability reservoirs under a combination of specific reservoir conditions. [ABSTRACT FROM AUTHOR]

CO2 pre-fracturing technology represents a novel approach to CO2 fracturing, effectively enhancing carbon capture efficiency in shale reservoirs while increasing the recovery of hydrocarbon resources. This study systematically quantifies the impact of water injection on the pore structure and permeability of shale samples saturated with pre-injected CO2. Based on X-ray diffraction (XRD) and low-temperature nitrogen adsorption (LT-NA) results, the dominant mechanism of the swelling-chemical coupling effect in shale property is clarified. Pre-injected CO2 can effectively mitigate the impact of water absorption. After a reaction time of 7 days, the permeability of the CO2-involved hydrated shale samples is four times that of samples without CO2. Nevertheless, the influence of subsequently injected water on shale permeability persists, resulting in an 80% reduction in shale permeability. XRD and LT-NA results indicate that the swelling-chemical coupling effect is the dominant factor in shale property variation during CO2 pre-fracturing. In the initial stage, the decline in calcite and clay mineral content is significant, and chemical dissolution dominates the change in pore structure. As the reaction progresses, the intensity of chemical reactions weakens, and clay mineral swelling becomes the primary factor affecting the shale properties. In this stage, K+ generated from original minerals effectively inhibits clay mineral swelling. Therefore, the swelling-chemical coupling effects should be comprehensively considered during the CO2 pre-fracturing process, and an appropriate soaking time should be selected to maximize CO2 storage efficiency and oil and gas production. [ABSTRACT FROM AUTHOR]