Hypericin enhances β-lactam antibiotics activity by inhibiting sarA expression in methicillin-resistant Staphylococcus aureus.

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)

Switching Behavior to Cloud Enterprise Information Systems in China

Cloud computing has recently become a popular information technology in China. Several China’s enterprises tend to move from client/server enterprise information systems (EISs) to cloud EISs. However, few studies have addressed the switching issues. This study aims to investigate factors that affect switching behavior from client/server EISs to cloud EISs. The research model draws from technology-organization-environment framework. We collected data from top managers and owners of China’s enterprises to analyze six hypotheses. The results show that technological context (perceived security and compatibility), and environmental context (supplier support and consultant support) significantly influence switching behavior. The findings are useful for understanding switching issues from client/server EISs to cloud EISs

Molecular Characterization of Magnesium Chelatase in Soybean [Glycine max (L.) Merr.]

Soybean (Glycine max) seed yields rely on the efficiency of photosynthesis, which is poorly understood in soybean. Chlorophyll, the major light harvesting pigment, is crucial for chloroplast biogenesis and photosynthesis. Magnesium chelatase catalyzes the insertion of Mg2+ into protoporphyrin IX in the first committed and key regulatory step of chlorophyll biosynthesis. It consists of three types of subunits, ChlI, ChlD, and ChlH. To gain a better knowledge of chlorophyll biosynthesis in soybean, we analyzed soybean Mg-chelatase subunits and their encoding genes. Soybean genome harbors 4 GmChlI genes, 2 GmChlD genes, and 3 GmChlH genes, likely evolved from two rounds of gene duplication events. The qRT-PCR analysis revealed that GmChlI, GmChlD, and GmChlH genes predominantly expressed in photosynthetic tissues, but the expression levels among paralogs are different. In silicon promoter analyses revealed these genes harbor different cis-regulatory elements in their promoter regions, suggesting they could differentially respond to various environmental and developmental signals. Subcellular localization analyses illustrated that GmChlI, GmChlD, and GmChlH isoforms are all localized in chloroplast, consistent with their functions. Yeast two hybrid and bimolecular fluorescence complementation (BiFC) assays showed each isoform has a potential to be assembled into the Mg-chelatase holocomplex. We expressed each GmChlI, GmChlD, and GmChlH isoform in Arabidopsis corresponding mutants, and results showed that 4 GmChlI and 2 GmChlD isoforms and GmChlH1 could rescue the severe phenotype of Arabidopsis mutants, indicating that they maintain normal biochemical functions in vivo. However, GmChlH2 and GmChlH3 could not completely rescue the chlorotic phenotype of Arabidopsis gun5-2 mutant, suggesting that the functions of these two proteins could be different from GmChlH1. Considering the differences shown on primary sequences, biochemical functions, and gene expression profiles, we conclude that the paralogs of each soybean Mg-chelatase subunit have diverged more or less during evolution. Soybean could have developed a complex regulatory mechanism to control chlorophyll content to adapt to different developmental and environmental situations

Clinical Evaluation of Targeted Arterial Infusion of Verapamil in the Interventional Chemotherapy of Primary Hepatocellular Carcinoma

This study evaluates the clinical effectiveness of targeted arterial infusion of verapamil in interventional treatment of primary hepatocellular carcinoma. For this purpose, in 273 patients with middle- or late-stage primary hepatocellular carcinoma, verapamil, IL-2, and chemotherapeutic agents were infused into the target tumor vasculature through femoral artery using Seldinger technique. The medications were infused as serial dilutions, and effectiveness was evaluated after two treatment cycles. Among these 273 patients, 76 cases showed clinical cure or significant improvement, 119 cases improved, 64 cases stabilized, while 14 cases progressed or deteriorated. In 238 patients, KPS score and body weights were stabilized. Regarding side effects, 99 patients (36.3%) developed leukopenia; 160 patients had gastrointestinal reactions (58.6%); 80 patients (29.3%) presented with elevated ALT/AST profile; and 65 cases (23.8%) had pyrexia; however, these side effects abated quickly. No elevations in BUN/Cr and/or allergic reactions were observed. Pre- and post-intervention cardiac function did not change in all the patients. No significant change was observed in ECG. Liver function was also improved after two cycles of treatment. It was concluded that verapamil management via targeted arterial infusion could effectively reverse the multidrug resistance in cancer cells in primary hepatocellular carcinoma patients and therefore enhanced the efficacy of chemotherapy

Subway Station Capacity Maintained by Optimizing a Maintenance Schedule of Key Equipment

The service capacity of each station has a direct impact on the capacity of a subway line and also the whole subway network. Therefore, it is critically important to keep the station capacity above a certain level in its full life cycle. This paper aims at keeping subway station capacity in a certain level range. In consideration of key equipment failure, the expected station capacity model is established. After that the lower bound of equipment reliability is determined by sensitivity analysis based on the equipment reliability-expected station capacity curve. Finally, the maintenance schedule optimization model is also proposed. The validity and practicability of the proposed method are demonstrated by a simulation case study

Experimental Study of Oil Displacement and Gas Channeling during CO2 Flooding in Ultra—Low Permeability Oil Reservoir

Aiming to solve the problems of poor CO2 displacement efficiency and serious gas-channeling and low well-opening rates in ultra-low permeability reservoirs, we carry out CO2 displacement experiments under different permeability reservoirs by using different development methods, water drive to gas drive procedures, and different fracture positions to clarify the effects of physical formation properties, injection methods, and fracture parameters on CO2 displacement efficiency in C8 ultra-low permeability reservoirs. The experimental results show that the recovery degree of CO2 miscible drive increases with an increase in permeability. When the gas–oil ratio is greater than 2000 m3/m3, serious gas channeling can be observed in both the miscible drive and immiscible drive. In addition, when the water drive is altered to be a gas drive, the water cut of 0.45 mD and 0.98 mD cores decreased, and the recovery degree increased by 13.4% and 16.57%, respectively. A long fracture length will deteriorate gas channeling and lower the CO2 oil-displacement efficiency. However, the fracture location is found to have little impact on the recovery of CO2 displacement

Experimental Study of Oil Displacement and Gas Channeling during CO₂ Flooding in Ultra—Low Permeability Oil Reservoir

Aiming to solve the problems of poor CO2 displacement efficiency and serious gas-channeling and low well-opening rates in ultra-low permeability reservoirs, we carry out CO2 displacement experiments under different permeability reservoirs by using different development methods, water drive to gas drive procedures, and different fracture positions to clarify the effects of physical formation properties, injection methods, and fracture parameters on CO2 displacement efficiency in C8 ultra-low permeability reservoirs. The experimental results show that the recovery degree of CO2 miscible drive increases with an increase in permeability. When the gas–oil ratio is greater than 2000 m3/m3, serious gas channeling can be observed in both the miscible drive and immiscible drive. In addition, when the water drive is altered to be a gas drive, the water cut of 0.45 mD and 0.98 mD cores decreased, and the recovery degree increased by 13.4% and 16.57%, respectively. A long fracture length will deteriorate gas channeling and lower the CO2 oil-displacement efficiency. However, the fracture location is found to have little impact on the recovery of CO2 displacement

Hypericin enhances β-lactam antibiotics activity by inhibiting sarA expression in methicillin-resistant Staphylococcus aureus.

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)

Correlation between obesity and clinicopathological characteristics in patients with papillary thyroid cancer: a study of 1579 cases: a retrospective study

Objective To explore the relationship between body mass index (BMI) and clinicopathological characteristics in patients with papillary thyroid carcinoma (PTC). Methods The clinical data of 1,579 patients with PTC, admitted to our hospital from May 2016 to March 2017, were retrospectively analyzed. According to the different BMI of patients, it can be divided into underweight recombination (BMI < 18.5 kg/m), normal body recombination (18.5 ≤ BMI < 24.0 kg/m2), overweight recombination (24.0 ≤ BMI < 28.0 kg/m2) and obesity group (BMI ≥ 28.0 kg/m2). The clinicopathological characteristics of PTC in patients with different BMIs group were compared. Results In our study, the risk for extrathyroidal extension (ETE), advanced T stage (T III/IV), and advanced tumor-node-metastasis stage (TNM III/IV) in the overweight group were higher, with OR (odds ratio) = 1.99(1.41–2.81), OR = 2.01(1.43–2.84), OR = 2.94(1.42–6.07), respectively, relative to the normal weight group. The risk for ETE and T III/IV stage in the obese group were higher, with OR = 1.82(1.23–2.71) and OR = 1.82(1.23–2.70), respectively, relative to the normal weight group. Conclusion BMI is associated with the invasiveness of PTC. There is a higher risk for ETE and TNM III/IV stage among patients with PTC in the overweight group and for ETE among patients with PTC in the obese group