Preparation and tribological properties of multi-layer graphene/silicon dioxide composites-based solid lubricant coatings at elevated temperatures.

The solid lubricating coatings have an important role in hot metal forming. However, traditional lubricants cannot be applied to the harsh working conditions. In this investigation, the novel solid lubricant coatings including multi-layer graphene (MLG)/silicon dioxide (SiO2) composites and sodium metaphosphate phosphate were prepared. The high-temperature tribological properties of the solid lubricant coatings were investigated by friction and wear tester. The experimental results showed that SiO2 nanoparticles were evenly grafted by sol-gel method on the surface of MLG, forming MLG/SiO2 composites. MLG/SiO2 composites presented excellent thermal stability at 800°C. In the range of 400-800°C, the average coefficients of friction (COFs) were decreased from 0.3936 to 0.3663, and then increased from 0.3663 to 0.4226. Based on the analysis of wear scar, the lubrication mechanisms of the solid lubricating coatings were proposed. The low interlayer shear of MLG and the ball bearing of SiO2 nanoparticles are the main reason for the reduction of COFs. In addition, the tribo-chemical reaction film formed on the frictional interface could protect the contact surfaces from severe damage. The findings would be beneficial for developing novel lubricants for hot metal forming process.

Cyanidin chloride protects mice from methicillin-resistant Staphylococcus aureus-induced pneumonia by targeting Sortase A.

Methicillin-resistant Staphylococcus aureus (MRSA) has been developing rapidly in recent years. It poses a severe peril to global health care, and the new strategies to against the MRSA is urgently needed. Sortase A (SrtA) regulates the anchoring of many surface proteins. Compounds repress Staphylococcus aureus (S. aureus) cysteine transpeptidase SrtA are considered adequate potent virulence inhibitors. Then, we describe the identification of an effective SrtA inhibitor, cyanidin chloride, a bioflavonoid compound isolated from various plants. It has a reversible inhibitory effect on SrtA activity at an IC50 of 21.91 µg/mL. As a SrtA inhibitor, cyanidin chloride antagonizes SrtA-related virulence phenotypes due to its breadth and specificity, including fibrinogen adhesion, A549 cell invasion, biofilm formation, and surface protein (SpA) anchoring. Subsequently, molecular docking and fluorescence quenching revealed that SrtA and cyanidin chloride had robust mutual affinity. Further mechanistic studies revealed that Arg-197, Gly-167, and Sep-116 were the key-binding sites mediating the interaction between SrtA and cyanidin chloride. Notably, a significant therapeutic effect of cyanidin chloride in vivo was also observed on the mouse pneumonia model induced by MRSA. In conclusion, our study indicates that cyanidin chloride potentially represents a new candidate SrtA inhibitor for S. aureus and potentially be developed as a new antivirulence agent.

Quercetin Reduces the Virulence of S. aureus by Targeting ClpP to Protect Mice from MRSA-Induced Lethal Pneumonia.

The dramatic increase of methicillin-resistant Staphylococcus aureus (MRSA) poses a great challenge to the treatment of Staphylococcus aureus (S. aureus) infections. Therefore, there is an urgent need to identify novel anti-infective agents to attack new targets to overcome antibiotic resistance. Casein hydrolase P (ClpP) is a key virulence factor in S. aureus to maintain cellular homeostasis. We screened from flavonoids and finally determined that quercetin could effectively attenuate the virulence of MRSA. The results of the thermal shift assay showed that quercetin could bind to ClpP and reduce the thermal stability of ClpP, and the KD value between quercetin and ClpP was 197 nM as determined by localized surface plasmon resonance. We found that quercetin exhibited a protective role of a mouse model of MRSA-induced lethal infection in a murine model. Based on the above facts, quercetin, as a ClpP inhibitor, could be further developed as a potential candidate for antivirulence agents to combat S. aureus infections. IMPORTANCE The resistance of Staphylococcus aureus (S. aureus) to various antibiotics has increased dramatically, and thus the development of new anti-infective drugs with new targets is urgently needed to combat resistance. Caseinolytic peptidase P (ClpP) is a casein hydrolase that has been shown to regulate a variety of important virulence factors in S. aureus. Here, we found that quercetin, a small-molecule compound from traditional Chinese herbal flavonoids, effectively inhibits ClpP activity. Quercetin attenuates the expression of multiple virulence factors in S. aureus and effectively protects mice from lethal pneumonia caused by MRSA. In conclusion, we determined that quercetin is a ClpP inhibitor and an effective lead compound for the development of a virulence factor-based treatment for S. aureus infection.

Tetrahedral Framework Nucleic Acid Delivered RNA Therapeutics Significantly Attenuate Pancreatic Cancer Progression via Inhibition of CTR1-Dependent Copper Absorption.

Copper is vital for various life processes, whereas severely toxic at excess level. Intracellular copper homeostasis is strictly controlled by a set of transporters and chaperones encoded by the copper homeostasis genes. Increasing evidence has shown that copper is usually overloaded in multiple malignancies, including pancreatic cancer, which has an extremely poor prognosis. Recently, silencing the SLC31A1 gene, which encodes a major transmembrane copper transporter (CTR1), has been demonstrated to be an effective means for reducing the malignant degree of pancreatic cancer by downregulating the cellular copper levels. Herein, we utilized tetrahedral framework nucleic acids (tFNAs) as vehicles to overcome the biological barriers for delivering small molecular RNAs and efficiently transferred two kinds of CTR1 mRNA-targeted RNA therapeutics, siCTR1 or miR-124, into PANC-1 cells. Both therapeutic tFNAs, termed t-siCTR1 and t-miR-124, prevented copper intake more effective than the free RNA therapeutics via efficiently suppressing the expression of CTR1, thereby significantly attenuating the progression of PANC-1 cells. In this study, therapeutic tFNAs are constructed to target metal ion transporters for the first time, which may provide an effective strategy for future treatment of other metal metabolism disorders.

[Prognostic factors of postoperative stroke in general and orthopedic surgeries: a nested case-control study].

OBJECTIVE: To evaluate the prognostic factors of postoperative stroke in general and orthopedic surgeries using a nested case-control design. METHODS: The retrieval of information was performed from the medical records database in the Peking University Third Hospital. A total of 596 records with stroke diagnosis from January 2009 to December 2011 were recruited as the study cases, among which 29 cases were diagnosed with stroke occurred postoperatively. 174 cases with similar surgical types, date of operation and anesthesia technique were explored as control group according to the principle of the nested case-control design. The data were analyzed using Logistic regression model. RESULTS: Univariate analysis showed that age, hypertension, diabetes, stroke or TIA history, non-atrial arrhythmias during surgery were prognostic factors for postoperative stroke. Logistic regression analysis showed that patients with stroke or TIA history, atrial fibrillation and age were independent prognostic factors for postoperative stroke, stroke or TIA history were the most significant factor associated with postoperative stroke (OR=13.01), followed by atrial fibrillation (OR=7.77) and age (OR=6.40). CONCLUSION: Stroke or TIA history, atrial fibrillation, and age are independent prognostic factors for postoperative stroke. Hypertension, diabetes, and non-atrial arrhythmias during surgery are prognostic factors for postoperative stroke.