A pentacyclic quinone diosindigo B from the heartwood of Diospyros melanoxylon

Diosindigo A, diosindigo B and biramentacéone have been isolated from heartwood of Diospyros melanoxylon. A violet pigment isolated from the same source has been shown to be a new pentacyclic quinone. Sunlight causes diosindigo B to change to the pentacyclic quinone and biramentacéone. The intense peaks at m/e 389 and 388 in the mass spectrum of diosindigo B are doublets which arise by fragmentation of both M⁺ and M⁺ + 2.     

Chemical shift assignments of domain 4 from the phosphohexomutase from Pseudomonas aeruginosa suggest that freeing perturbs its coevolved domain interface

A domain needed for the catalytic efficiency of an enzyme model of simple processivity and domain–domain interactions has been characterized by NMR. This domain 4 from phosphomannomutase/phosphoglucomutase (PMM/PGM) closes upon glucose phosphate and mannose phosphate ligands in the active site, and can modestly reconstitute activity of enzyme truncated to domains 1–3. This enzyme supports biosynthesis of the saccharide-derived virulence factors (rhamnolipids, lipopolysaccharides, and alginate) of the opportunistic bacterial pathogen Pseudomonas aeruginosa. ¹H, ¹³C, and ¹⁵N NMR chemical shift assignments of domain 4 of PMM/PGM suggest preservation and independence of its structure when separated from domains 1–3. The face of domain 4 that packs with domain 3 is perturbed in NMR spectra without disrupting this fold. The perturbed residues overlap both the most highly coevolved positions in the interface and residues lining a cavity at the domain interface.     

Development of Diagnostic Microscopic and Chemical Markers of Some Euphorbia Latexes

The latexes of the three Euphorbia species, namely E. antiquorum L., E. nerifolia L., and E. tirucalli L., are highly valued in the Indian system of medicine as purgatives, in addition to their specific and distinct therapeutic activities. In order to distinguish these latexes and develop their diagnostic microscopic and chemical markers, we performed extensive chemical and microscopic studies. The three latexes differ significantly in their microscopic features by exhibiting characteristic starch grain patterns. Although amoebic structures were found to be characteristic of E. antiquorum, dumb-bell and oval structures are characteristic of E. nerifolia and E. tirucalli, respectively. In addition, these latexes showed bone-shaped structures as a common feature, but these differed considerably in their length （10-60, 30-55, and 50-70 μm in length in E. antiquorum, E. nerifolia, and E. tirucalli, respectively）. The chemical markers nerifoliene and euphol were found to be common to both E. antiquorum and E. nerifolia, whereas euphol is the only marker for E. tirucalli. A reverse-phase high-performance thin-layer chromatographic （HPTLC） method was developed to distinguish these three latexes and to generate their standard fingerprinting patterns. Most significantly, the markers nerifoliene and euphol could be resolved by RP-18 F254s precoated aluminium plates and the latexes have been quantitatively estimated with respect to these markers. The developed microscopic, chemical and HPTLC patterns can be used to distinguish the three latexes.     

HipA-Triggered Growth Arrest and β-Lactam Tolerance in Escherichia coli Are Mediated by RelA-Dependent ppGpp Synthesis

Persistence is a phenomenon whereby a subpopulation of bacterial cells enters a transient growth-arrested state that confers antibiotic tolerance. While entrance into persistence has been linked to the activities of toxin proteins, the molecular mechanisms by which toxins induce growth arrest and the persistent state remain unclear. Here, we show that overexpression of the protein kinase HipA in Escherichia coli triggers growth arrest by activating synthesis of the alarmone guanosine tetraphosphate (ppGpp) by the enzyme RelA, a signal typically associated with amino acid starvation. We further demonstrate that chemically suppressing ppGpp synthesis with chloramphenicol relieves inhibition of DNA replication initiation and RNA synthesis in HipA-arrested cells and restores vulnerability to β-lactam antibiotics. HipA-arrested cells maintain glucose uptake and oxygen consumption and accumulate amino acids as a consequence of translational inhibition. We harness the active metabolism of HipA-arrested cells to provide a bacteriophage-resistant platform for the production of biotechnologically relevant compounds, which may represent an innovative solution to the costly problem of phage contamination in industrial fermentations.     

Safety and Efficacy of Apixaban versus warfarin in patients with atrial fibrillation or Venous Thromboembolism and End-Stage renal disease on hemodialysis: A systematic review and meta-analysis

BackgroundWarfarin is traditionally the drug of choice for stroke prophylaxis or treatment of venous thromboembolism in patients with end-stage renal disease (ESRD) on hemodialysis as data on apixaban use is scarce. We aimed to assess the safety and efficacy of Apixaban in patients with ESRD on hemodialysis when compared with warfarin.MethodsA comprehensive literature search in PubMed, Google Scholar, and Cochrane databases from inception until Nov 25, 2019, was performed. Studies reporting clinical outcomes comparing Apixaban (2.5 mg BID or 5 mg BID) versus Warfarin in ESRD patients on hemodialysis were included. Mantel-Haenszel risk ratio (RR) random-effects model was used to summarize data.ResultsFour studies (three retrospective and one randomized) with a total of 9862 patients (apixaban = 2,547, warfarin = 7315) met inclusion criteria. The overall mean age was 66.6 ± 3.9 years and mean CHA2DS2-VASc score 4.56 ± 0.58. Apixaban was associated with lower rates of major bleeding (RR 0.53, 95% CI 0.45–0.64, p < 0.0001], gastrointestinal (GI) bleed (RR 0.65, 95% CI 0.55–0.76, p < 0.0001), intracranial bleed (RR 0.56, 95% CI 0.36–0.89, p = 0.01), and stroke/systemic embolism [RR 0.65, 95% CI 0.52–0.83, p = 0.0004] compared with warfarin in patients with ESRD on hemodialysis. There was no significant increased risk of all-cause mortality with the apixaban vs. warfarin (RR 0.90, 95% CI 0.41–1.96, p = 0.78).ConclusionApixaban had an overall favorable risk-benefit profile, with significant reductions in ischemic stroke, major bleeding, and intracranial bleeding compared to Warfarin in ESRD patients on hemodialysis with non-valvular AF and/or venous thromboembolism.     

Comparative life cycle assessment of smartphone reuse: repurposing vs. refurbishment

Purpose

Waste management for end-of-life (EoL) smartphones is a growing problem due to their high turnover rate and concentration of toxic chemicals. The versatility of modern smartphones presents an interesting alternative waste management strategy: repurposing. This paper investigates the environmental impact of smartphone repurposing as compared to traditional refurbishing using Life Cycle Assessment (LCA).

Methods

A case study of repurposing was conducted by creating a smartphone “app” that replicates the functionality of an in-car parking meter. The environmental impacts of this prototype were quantified using waste management LCA methodology. Studied systems included three waste management options: traditional refurbishment, repurposing using battery power, and repurposing using a portable solar charger. The functional unit was defined as the EoL management of a used smartphone. Consequential system expansion was employed to account for secondary functions provided; avoided impacts from displaced primary products were included. Impacts were calculated in five impact categories. Break-even displacement rates were calculated and sensitivity to standby power consumption were assessed.

Results and discussion

LCA results showed that refurbishing creates the highest environmental impacts of the three reuse routes in every impact category except ODP. High break-even displacement rates suggest that this finding is robust within a reasonable range of primary cell phone displacement. The repurposed smartphone in-car parking meter had lower impacts than the primary production parking meter. Impacts for battery-powered devices were dominated by use-phase charging electricity, whereas solar-power impacts were concentrated in manufacturing. Repurposed phones using battery power had lower impacts than those using solar power, however, standby power sensitivity analysis revealed that solar power is preferred if the battery charger is left plugged-in more than 20 % of the use period.

Conclusions

Our analysis concludes that repurposing represents an environmentally preferable EoL option to refurbishing for used smartphones. The results suggest two generalizable findings. First, primary product displacement is a major factor affecting whether any EoL strategy is environmentally beneficial. The benefit depends not only on what is displaced, but also on how much displacement occurs; in general, repurposing allows freedom to target reuse opportunities with high “displacement potential.” Second, the notion that solar power is preferable to batteries is not always correct; here, the rank-order is sensitive to assumptions about user behavior.     

A diversity-oriented synthesis approach to macrocycles via oxidative ring expansion

Macrocycles are key structural elements in numerous bioactive small molecules and are attractive targets in the diversity-oriented synthesis of natural product-based libraries. However, efficient and systematic access to diverse collections of macrocycles has proven difficult using classical macrocyclization reactions. To address this problem, we have developed a concise, modular approach to the diversity-oriented synthesis of macrolactones and macrolactams involving oxidative cleavage of a bridging double bond in polycyclic enol ethers and enamines. These substrates are assembled in only four or five synthetic steps and undergo ring expansion to afford highly functionalized macrocycles bearing handles for further diversification. In contrast to macrocyclization reactions of corresponding seco acids, the ring expansion reactions are efficient and insensitive to ring size and stereochemistry, overcoming key limitations of conventional approaches to systematic macrocycle synthesis. Cheminformatic analysis indicates that these macrocycles access regions of chemical space that overlap with natural products, distinct from currently targeted synthetic drugs.     

New sesquiterpenoids of Bombax malabaricum

Hemigossypol-6-methyl ether, reported to be present in the root bark of Bombax malabaricum, has been shown to be isohemigossypol-1-methyl ether. Isohemigossypol-1,2-dimethyl ether, 8-formyl-7-hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4-naphthaquinone, 7-hydroxycadalene and an unidentified phenolic compound have also been isolated. Long range couplings in the ¹H NMR spectrum of isohemigossypol-1-methyl ether have been established by decoupling experiments.