Chemoselective Cross-Coupling Reactions as Tools in Synthesis and Applications for Polymer Chemistry

A nucleophile-selective cross-coupling reaction with vinyl and alkynyl bromides on a dinucleophilic thiophene bearing two metal groups, a boronic ester and a stannyl group, has been developed. The first nucleophilic site to react is the stannyl group, and subsequently, a Suzuki–Miyaura cross-coupling takes place after adding a second electrophile, base and water. The generality of the reaction was shown with various electron rich, electron neutral, electron poor vinyl bromides and alkynyl bromides. The roles typical in Sonogashira couplings or Heck reactions of the aromatic ring as the dielectrophile coupling to vinyl and alkynyl metal species are reversed, which presents a new tool for organic synthesis. Four different difunctional thienylpyrrole monomers with a bromide group on the thienyl moiety and a metal group (Mg, B, Sn or Zn) on the pyrrole moiety were developed. Based on those monomers, π-conjugated poly(thiophene-alt-pyrrole)s PTPs were firstly synthesized via nickel and palladium catalyzed Kumada polycondensation from this A-B type monomer. The polymers were analyzed by NMR, IR, GPC, MALDI-MS, UV-vis, PL and TGA measurements

Effects of ClpP protease on biofilm formation of Enterococcus faecalis

Enterococcus faecalis (E. faecalis), one of the main pathogens responsible for refractory periapical periodontitis and nosocomial infections, exhibits markedly higher pathogenicity in biofilms. Objectives: Studies have shown that caseinolytic protease P (ClpP) is involved in biofilm formation. However, to date, few studies have investigated the role of ClpP in the survival of E. faecalis, and in enhancing biofilm formation. Therefore, we investigated the role of ClpP in the formation of E. faecalis biofilms. Methodology: In our study, we used homologous recombination to construct clpP deleted and clpP complement strains of E. faecalis ATCC 29212. A viable colony counting method was used to analyze the growth patterns of E. faecalis. Crystal violet staining (CV) and confocal scanning laser microscopy (CLSM) were used to characterize biofilm mass formation and scanning electron microscopy (SEM) was used to observe the biofilm microstructure. Data was statistically analyzed via Student’s t-test or one-way analysis of variance (ANOVA). Results: The results exhibited altered growth patterns for the clpP deletion strains and depleted polysaccharide matrix, resulting in reduced biofilm formation capacity compared to the standard strains. Moreover, ClpP was observed to increase biofilm formation in E. faecalis. Conclusion: Our study shows that ClpP can increase biofilm formation in E. faecalis and emphasizes the importance of ClpP as a potential target against E. faecalis

m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade

Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N6-methyladenosine (m6A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma (IFNγ) and sensitizes melanoma to anti-PD-1 treatment in mice, depending on adaptive immunity. Our findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade may reduce the resistance to immunotherapy in melanoma. © 2019, The Author(s)

Effects of Antibacterial Peptide Extracted from Bacillus subtilis fmbJ on the Growth, Physiological Response and Disease Resistance of Megalobrama amblycephala

The effects of an antibacterial peptide obtained from Bacillus subtilis fmbJ on growth, serum lysozyme complements 3 and 4, total protein content, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total antioxidative capacity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and disease resistance of Wuchang bream (Megalobrama amblycephala) were examined. Fish were randomly divided into five groups: a control group which was fed a basic diet, and four groups fed the basic diet supplemented with 0.1%, 0.2%, 0.4%, or 0.8% antibacterial peptide. At eight weeks, M. amblycephala fed the diet containing 0.2% antibacterial peptide had higher serum lysozyme activity, complement 3 and 4 contents, and SOD activity than the control fish, but lower serum MDA content and AST activity. Fish fed the 0.4% diet had higher weight gain rate, serum lysozyme activity, complement 4 content, total antioxidative capacity, and total protein than the control, and lower serum ALT activity. Feed conversion ratios of fish fed the 0.2% or 0.4% diets were lower than those of control fish. Artificial infection with Aeromonas hydrophila resulted in 93% cumulative mortality in the control group, and 61-84% in the groups fed the 0.2% or 0.4% diets. The present study suggests that feed supplementation with 0.2-0.4% antibacterial peptides can stimulate immunity, increase resistance to pathogenic infection, and promote growth in M. amblycephala

Improving the Exchange of Lessons Learned in Security Incident Reports: Case Studies in the Privacy of Electronic Patient Records

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. This is an Open Access article.The increasing use of Electronic Health Records has been mirrored by a similar rise in the number of security incidents where con fidencial information has inadvertently been disclosed to third parties. These problems have been compounded by an apparent inability to learn from previous violations; similar security incidents have been observed across Europe, North America and Asia. This has resulted in the loss of con fidence and trust of the public towards the organisations' ability to protect the patients' private information. The Generic Security Template (G.S.T.) has been proposed to communicate security lessons learned from previous security incidents. This paper conducts a series of empirical studies to evaluate the usability of the G.S.T. The first study compares the G.S.T. with the conventional text-based security incident reports. The two methods were compared in term of the users' ability to identify a number of lessons learned from investigations into previous incidents involving the disclosure of healthcare records. The study showed that the graphical approach resulted in higher accuracy in terms of number of correct answers generated by participants. However, subjective feedback raised further questions about the usability of the G.S.T. as the readers of security incident reports try to interpret the lessons that can increase the security of patient data. The second study further evaluates the usability of the G.S.T. using the Cognitive Dimensions and identifi es some aspects that need to be improved

Time-varying Reliability Analysis of Long-span Continuous Rigid Frame bridge under Cantilever Construction Stage based on the Monitored Strain Data

Abstract: In general, the material properties, loads, resistance of the prestressed concrete continuous rigid frame bridge in different construction stages are time-varying. So, it is essential to monitor the internal force state when the bridge is in construction. Among them, how to assess the safety is one of the challenges. As the continuous monitoring over a long-term period can increase the reliability of the assessment, so, based on a large number of monitored strain data collected from the structural health monitoring system (SHMS) during construction, a calculation method of the punctiform time-varying reliability is proposed in this paper to evaluate the stress state of this type bridge in cantilever construction stage by using the basic reliability theory. At the same time, the optimal stress distribution function in the bridge mid-span base plate is determined when the bridge is closed. This method can provide basis and direction for the internal force control of this type bridge in construction process. So, it can reduce the bridge safety and quality accidents in construction stages