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Aluminium phosphide (ALP) and aluminium zinc phosphide (ZnP), the two main ingredients of fumigation drugs, are commonly used to kill insects or rodents in grain. When exposed to water, highly toxic phosphine gas is released and absorbed through the respiratory or digestive tract. Phosphine gas could non-selectively block cytochrome oxidase, inhibit electron transfer and suppress oxidative phosphorylation, leading to cellular hypoxia and organ dysfunction. The characteristic clinical manifestations are refractory shock and metabolic acidosis with high mortality. However, patients with ALP poisoning have a chance to be cured. Here, we report a case of oral ALP poisoning that was successfully treated by extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) during frequent ventricular fibrillation and cardiac dysfunction.

Las lecciones de Chino paso a paso II permiten al estudiante aprender y ejercitar el chino mandarín. Gracias a ejercicios especiales podrá practicar la lectura de ensayos, la escritura de los distintos caracteres y la escucha y comprensión gracias a canciones y poemas que permiten experimentar el ritmo del idioma. Los dos libros que componen Chino paso a paso II facilitan el aprendizaje de las habilidades exigidas en el examen internacional de chino mandarín HSK. Esta es la continuación del libro de texto Chino paso a paso I, que en el 2010 ganó el premio a la excelencia en la categoría de material internacional de enseñanza del chino mandarín, por Hanban, la Oficina Central del Instituto Confucio (institución que promueve la enseñanza del chino, con sede en Beijing). Huijing Zhang y Mingjun Yuan

Antibiotic resistance threatens effective treatment of microbial infections globally. This situation has spurred the hunt for new antimicrobial compounds in both academia and the pharmaceutical industry. Here, we report how the widely used antitumor drug cisplatin may be repurposed as an effective antimicrobial against the nosocomial pathogen Pseudomonas aeruginosa. Cisplatin was found to effectively kill strains of P. aeruginosa. In such experiments, transcriptomic profiling showed upregulation of the recA gene, which is known to be important for DNA repair, implicating that cisplatin could interfere with DNA replication in P. aeruginosa. Cisplatin treatment significantly repressed the type III secretion system (T3SS), which is important for the secretion of exotoxins. Furthermore, cisplatin was also demonstrated to eradicate in vitro biofilms and in vivo biofilms in a murine keratitis model. This showed that cisplatin could be effectively used to eradicate biofilm infections which were otherwise difficult to be treated by conventional antibiotics. Although cisplatin is highly toxic for humans upon systemic exposure, a low toxicity was demonstrated with topical treatment. This indicated that higher-than-minimal inhibitory concentration (MIC) doses of cisplatin could be topically applied to treat persistent and recalcitrant P. aeruginosa infections.

In this study,an implantable optrode was developed for optogenetics stimulation of neural population in nuclei or multi-sites in neural circuits.The optrode was composed of base layer,micro-light emitting diode(LED)and coating layer.The base layer was a 150μm thick polyimide substrate on which copper wires and contacts were fabricated by flexible printed circuit board processes.The micro-LED was soldered on the contacts using SnBi.ParyleneC was deposited over the optrode as the coating layer using a vacuum vapor deposition system.The optical output power was tested by optical power meter and the insulating property was tested using saline in the experiment.The stimulation function of the optrode was demonstrated through animal experiment.The width of the optrode was500μm and the maximum thickness of the optrode was 310μm at the LED position.The thickness of the parylene coating layer was about 1μm.The maximum optical output power of optrode was 9.31 mW and the effective illumination area was a 3.03mm2 spherical cap at 650μm deep in brain tissue.The optrode was still functional after 14 days in physiological saline.Conventional copper electrodes were used to verify the efficacy of the optrode for stimulation and robust spiking activities of the expressing Channelrhodopsin-2neurons in the entire cortex of a mouce were recorded.Obvious behavior change happened when light stimulation was applied to the expressing Channelrhodopsin-2neurons in the secondary motor cortex of the mice.The optrode has the characteristics of large effective illumination range,flexible in implantation and long-term implantable,which provide neural population in nuclei research a new tool.

Summary The nucleotide signalling molecule bis-(3'-5’)-cyclic dimeric guanosine monophosphate (c-di-GMP) plays an essential role in regulating microbial virulence and biofilm formation. C-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and degraded by phosphodiesterase (PDE) enzymes. One intrinsic feature of c-di-GMP signalling is the abundance of DGCs and PDEs encoded by many bacterial species. It is unclear whether the different DGCs or PDEs coordinately establish the c-di-GMP regulation or function independently of each other. Here, we provide evidence that multiple DGCs are involved in regulation of c-di-GMP on synthesis of the major iron siderophore pyoverdine in Pseudomonas aeruginosa. Constitutive expression of the WspG or YedQ DGC in P. aeruginosa is able to induce its pyoverdine synthesis. Induction of pyoverdine synthesis by high intracellular c-di-GMP depends on the synthesis of exopolysaccharides and another two DGCs, SiaD and SadC. SiaD was found to boost the c-di-GMP synthesis together with constitutively expressing YedQ. The exopolysaccharides and the SiaD DGC were found to modulate the expression of the RsmY/RsmZ ncRNAs. Induction of the RsmY/RsmZ ncRNAs might enhance the pyoverdine synthesis through SadC. Our study sheds light on a novel multiple DGC-coordinated c-di-GMP regulatory mechanism of bacteria.

Since its discovery 22 years ago, the bacterial cell-to-cell communication system, termed quorum sensing (QS), has shown potential as antipathogenic target. Previous studies reported that ajoene from garlic inhibits QS in opportunistic human pathogen Pseudomonas aeruginosa. In this study, screening of an in-house compound library revealed two sulfur-containing compounds which possess structural resemblance with ajoene and inhibit QS in bioreporter assay. Following a quantitative structure–activity relationship (SAR) study, 25 disulfide bond-containing analogues were synthesized and tested for QS inhibition activities. SAR study indicated that the allyl group could be replaced with other substituents, with the most active being benzothiazole derivative (IC50 = 0.56 μM). The compounds were able to reduce QS-regulated virulence factors (elastase, rhamnolipid, and pyocyanin) and successfully inhibit P. aeruginosa infection in murine model of implant-associated infection. Altogether, the QS inhibition activity of the synthesized compounds is encouraging for further exploration of novel analogues in antimicrobial drug development. MOE (Min. of Education, S’pore) NRF (Natl Research Foundation, S’pore)

Bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) is a global secondary bacterial messenger that controls the formation of drug-resistant multicellular biofilms. Lowering the intracellular c-di-GMP content can disperse biofilms, and it is proposed as a biofilm eradication strategy. However, freshly dispersed biofilm cells exhibit a physiology distinct from biofilm and planktonic cells, and they might have a clinically relevant role in infections. Here we present in vitro and in vivo protocols for the generation and characterization of dispersed cells from Pseudomonas aeruginosa biofilms by reducing the intracellular c-di-GMP content through modulation of phosphodiesterases (PDEs). Unlike conventional protocols that demonstrate biofilm dispersal by biomass quantification, our protocols enable physiological characterization of the dispersed cells. Biomarkers of dispersed cells are identified and quantified, serving as potential targets for treating the dispersed cells. The in vitro protocol can be completed within 4 d, whereas the in vivo protocol requires 7 d. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Accepted version

Stress response plays an important role on microbial adaptation under hostile environmental conditions. It is generally unclear how the signaling transduction pathway mediates a stress response in planktonic and biofilm modes of microbial communities simultaneously. Here, we showed that metalloid tellurite (TeO32–) exposure induced the intracellular content of the secondary messenger cyclic di-GMP (c-di-GMP) of Pseudomonas aeruginosa. Two diguanylate cyclases (DGCs), SadC and SiaD, were responsible for the increased intracellular content of c-di-GMP. Enhanced c-di-GMP levels by TeO32– further increased P. aeruginosa biofilm formation and resistance to TeO32–. P. aeruginosa ΔsadCΔsiaD and PAO1/plac-yhjH mutants with low intracellular c-di-GMP content were more sensitive to TeO32– exposure and had low relative fitness compared to the wild-type PAO1 planktonic and biofilm cultures exposed to TeO32–. Our study provided evidence that c-di-GMP level can play an important role in mediating stress response in microbial communities during both planktonic and biofilm modes of growth.