The Assessment on Synergistic Activity of Ebselen and Silver Ion Against Yersinia pseudotuberculosis

Yersinia pseudotuberculosis is a foodborne zoonotic bacterium that is pathogenic to guinea pigs, rabbits, and mice. It also causes pseudotuberculosis in humans. However, it still lacked the scientific basis for control. Here, we found out that Ebselen (EbSe) exhibited synergistic antibacterial activity with silver nitrate (Ag+) against Y. pseudotuberculosis YpIII strain with high efficacy in vitro using UV-visible light absorption spectrum, 5,5’-dithiobis-(2-nitrobenzoic acid), laser scanning confocal microscope, flow cytometry, transmission electron microscopy and Western blotting assays. The depletion of total glutathione (GSH) amount and inhibition of thioredoxin reductase (TrxR) activity in thiol-dependent redox system revealed the destructiveness of EbSe-Ag+-caused intracellular oxidative stress. Furthermore, a YpIII-caused mice gastroenteritis model was constructed. EbSe-Ag+ significantly reduced bacterial loads with low toxicity. It also down-regulated the expression levels of interferon (IL)-1β and tumor necrosis factor-α, up-regulated the expression level of IL-10 on-site. All the in vivo results demonstrated the antibacterial activity and immune-modulatory property of EbSe-Ag+. Collectively, these results provided academic fundament for further analysis and development of EbSe-Ag+ as the antibacterial agents for pseudotuberculosis control

Advanced lung cancer inflammation index is associated with long-term cardiovascular death in hypertensive patients: national health and nutrition examination study, 1999–2018

Background: Hypertension is one of the main causes of cardiovascular death. Inflammation was considered influential factors of cardiovascular (CVD) death in patients with hypertension. Advanced lung cancer inflammation index (ALI) is an index to assess inflammation, few studies have investigated the relationship between advanced lung cancer inflammation index and cardiovascular death in hypertensive patients.Objective: The aim of this study was to investigate the association between advanced lung cancer inflammation index and long-term cardiovascular death in hypertensive patients.Method: Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 with mortality follow-up through 31 December 2019 were analyzed. Advanced lung cancer inflammation index was calculated as BMI (kg/㎡) × serum albumin level (g/dL)/neutrophil to lymphocyte ratio (NLR). A total of 20,517 participants were evaluated. Patients were divided into three groups based on tertiles of advanced lung cancer inflammation index as follows: T1 (n = 6,839), T2 (n = 6,839), and T3 (n = 6,839) groups. The relationship between advanced lung cancer inflammation index and long-term cardiovascular death was assessed by survival curves and Cox regression analysis based on the NHANES recommended weights.Results: The median advanced lung cancer inflammation index value in this study was 61.9 [44.4, 84.6]. After full adjustment, the T2 group (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.50–0.69; p < 0.001) and T3 group (HR: 0.48, 95% CI: 0.39–0.58; p < 0.001) were found to have a significantly lower risk of cardiovascular death compared to the T1 group.Conclusion: High levels of advanced lung cancer inflammation index were associated with reduced risk of cardiovascular death in hypertensive patients

Interfacial reaction and mechanical properties of diffusion bonded titanium/17-4 PH stainless steel dissimilar joint using a silver interlayer

Diffusion bonding of titanium (Ti) to 17-4 PH high strength stainless steel is challenging owing to the formation of brittle Ti-Fe intermetallic compounds (IMCs) at joint interface. In the current study, it was demonstrated that such detrimental Ti-Fe IMCs can be effectively eradicated by using a silver (Ag) interlayer. The diffusion bonded Ti/Ag/17-4 PH stainless steel is characterized by Ti-Ag solid solution, TiAg, remnant Ag interlayer and Ag-(Fe, Cr, Ni) interdiffusion layer. The interfacial reaction phase TiAg exhibited no detrimental effect on bonding strength. During tensile test, ductile fracture took place in the remaining Ag interlayer of resultant joint. Bonding strength up to ∼420 MPa was obtained over bonding durations in the range of 15 ∼ 25 min. It is thus concluded that using an Ag interlayer is highly appealing in improving bonding strength of diffusion bonded Ti/17-4 PH stainless steel dissimilar joint

Invasive intracranial aspergillosis spread by the pterygopalatine fossa in an immunocompetent patient

Aspergillosis of the central nervous system (CNS) is an uncommon infection, mainly found in immunocompromised patients but rarely seen among immunocompetent patients. Herein we describe a 57 year-old immunocompetent man who suffered intracranial aspergillosis spread by the pterygopalatine fossa (PPF) following a tooth extraction. Based on magnetic resonance imaging (MRI) characteristics, in this report we focus on the spreading routes of CNS aspergillosis via communicative structures of the PPF, the relationship between clinical manifestations and the locations of the lesion, and propose a therapeutic strategy to improve the prognosis

The Assessment on Synergistic Activity of Ebselen and Silver Ion Against Yersinia pseudotuberculosis

Yersinia pseudotuberculosis is a foodborne zoonotic bacterium that is pathogenic to guinea pigs, rabbits, and mice. It also causes pseudotuberculosis in humans. However, it still lacked the scientific basis for control. Here, we found out that Ebselen (EbSe) exhibited synergistic antibacterial activity with silver nitrate (Ag+) against Y. pseudotuberculosis YpIII strain with high efficacy in vitro using UV-visible light absorption spectrum, 5,5’-dithiobis-(2-nitrobenzoic acid), laser scanning confocal microscope, flow cytometry, transmission electron microscopy and Western blotting assays. The depletion of total glutathione (GSH) amount and inhibition of thioredoxin reductase (TrxR) activity in thiol-dependent redox system revealed the destructiveness of EbSe-Ag+-caused intracellular oxidative stress. Furthermore, a YpIII-caused mice gastroenteritis model was constructed. EbSe-Ag+ significantly reduced bacterial loads with low toxicity. It also down-regulated the expression levels of interferon (IL)-1β and tumor necrosis factor-α, up-regulated the expression level of IL-10 on-site. All the in vivo results demonstrated the antibacterial activity and immune-modulatory property of EbSe-Ag+. Collectively, these results provided academic fundament for further analysis and development of EbSe-Ag+ as the antibacterial agents for pseudotuberculosis control

Table_1_Breaking down the cell wall: Still an attractive antibacterial strategy.DOCX

Since the advent of penicillin, humans have known about and explored the phenomenon of bacterial inhibition via antibiotics. However, with changes in the global environment and the abuse of antibiotics, resistance mechanisms have been selected in bacteria, presenting huge threats and challenges to the global medical and health system. Thus, the study and development of new antimicrobials is of unprecedented urgency and difficulty. Bacteria surround themselves with a cell wall to maintain cell rigidity and protect against environmental insults. Humans have taken advantage of antibiotics to target the bacterial cell wall, yielding some of the most widely used antibiotics to date. The cell wall is essential for bacterial growth and virulence but is absent from humans, remaining a high-priority target for antibiotic screening throughout the antibiotic era. Here, we review the extensively studied targets, i.e., MurA, MurB, MurC, MurD, MurE, MurF, Alr, Ddl, MurI, MurG, lipid A, and BamA in the cell wall, starting from the very beginning to the latest developments to elucidate antimicrobial screening. Furthermore, recent advances, including MraY and MsbA in peptidoglycan and lipopolysaccharide, and tagO, LtaS, LspA, Lgt, Lnt, Tol-Pal, MntC, and OspA in teichoic acid and lipoprotein, have also been profoundly discussed. The review further highlights that the application of new methods such as macromolecular labeling, compound libraries construction, and structure-based drug design will inspire researchers to screen ideal antibiotics.</p

Single-Stranded DNA Cleavage by Divergent CRISPR-Cas9 Enzymes

Double-stranded DNA (dsDNA) cleavage by Cas9 is a hallmark of type II CRISPR-Cas immune systems. Cas9–guide RNA complexes recognize 20-base-pair sequences in DNA and generate a site-specific double-strand break, a robust activity harnessed for genome editing. DNA recognition by all studied Cas9 enzymes requires a protospacer adjacent motif (PAM) next to the target site. We show that Cas9 enzymes from evolutionarily divergent bacteria can recognize and cleave single-stranded DNA (ssDNA) by an RNA-guided, PAM-independent recognition mechanism. Comparative analysis shows that in contrast to the type II-A S. pyogenes Cas9 that is widely used for genome engineering, the smaller type II-C Cas9 proteins have limited dsDNA binding and unwinding activity and promiscuous guide-RNA specificity. These results indicate that inefficiency of type II-C Cas9 enzymes for genome editing results from a limited ability to cleave dsDNA, and suggest that ssDNA cleavage was an ancestral function of the Cas9 enzyme family