Growing evidence suggests the existence of new antibiotic resistance mechanisms. Recent studies have revealed that quorum-quenching enzymes, such as MacQ, are involved in both antibiotic resistance and cell-cell communication. Furthermore, some small bacterial regulatory RNAs, classified into RNA attenuators and small RNAs, modulate the expression of resistance genes. For example, small RNA sprX, can shape bacterial resistance to glycopeptide antibiotics via specific downregulation of protein SpoVG. Moreover, some bacterial lipocalins capture antibiotics in the extracellular space, contributing to severe multidrug resistance. But this defense mechanism may be influenced by Agr-regulated toxins and liposoluble vitamins. Outer membrane porin proteins and efflux pumps can influence intracellular concentrations of antibiotics. Alterations in target enzymes or antibiotics prevent binding to targets, which act to confer high levels of resistance in respiratory/oral bacteria. As described recently, horizontal gene transfer, including conjugation, transduction and transformation, is common in respiratory/oral microflora. Many conjugative transposons and plasmids discovered to date encode antibiotic resistance proteins and can be transferred from donor bacteria to transient recipient bacteria. New classes of mobile genetic elements are also being identified. For example, nucleic acids that circulate in the bloodstream (circulating nucleic acids) can integrate into the host cell genome by up-regulation of DNA damage and repair pathways. With multidrug resistant bacteria on the rise, new drugs have been developed to combate bacterial antibiotic resistance, such as innate defense regulators, reactive oxygen species and microbial volatile compounds. This review summaries various aspects and mechanisms of antibiotic resistance in the respiratory/oral microbiota. A better understanding of these mechanisms will facilitate minimization of the emergence of antibiotic resistance.
Small interfering RNA (siRNA) has become a powerful tool for selectively silencing gene expression in cultured mammalian cells. In this study, a 67-bp oligonucleotide encoding human telomerase RNA (hTR) was introduced into pSIREN, a shuttle vector for construction of recombinant adenovirus. Then the U6-RNA promoter and siRNA-encoding insert were cut out from the pSIREN and subcloned into pAdeno-X to construct the plasmid pAd-hTR. After the pAd-hTR was transfected into a mammalian cell line HEK-293, adenovirus carrying the hTR-targeting siRNA (Ad-hTR-siRNA) was obtained. We performed a series of experiments to demonstrate silencing of the telomerase mediated by Ad-hTR-siRNA in HeLa cells. Compared with control virus (Ad-NT-siRNA), Ad-hTR-siRNA significantly reduced both hTR mRNA level (by 70.21%) and telomerase activity (by 58.87%) in HeLa cells. Moreover, it induced apoptosis in HeLa cells. Treatment of subcutaneous tumor xenografted with Ad-hTR-siRNA could slow down tumor growth, at least partially due to the induction of apoptosis (Po0.05) in vivo. Taken together, our results demonstrated efficient and specific knockdown of telomerase in HeLa cell line by the hTR siRNA, and indicated the prospect of applying this siRNA expressing recombinant adenovirus system in cancer gene therapy.
Conceptual design is the most creative stage in the product design process. This paper studies the idea generation process and the representation of design knowledge at the conceptual design stage and proposes an idea generation process model and a design unit model. Based on this and through analysing both conscious thought and the subconscious this paper proposes a mechanism of product idea generation, which has three types of cognition stimulation: extension stimulation, analogy stimulation, and mutation stimulation. Through exploring design methods and tools for implementing cognition stimulation, a conceptual design method is constructed, which focuses on carrying out the mechanism of idea generation. This method embodies in a systematic and effective manner the cognitive process and characteristics of the designer, incorporates product design knowledge, and assists the designer to generate a comprehensive conceptual design proposal. An example is presented to illustrate the principles of the proposed method. The process model and method proposed here should act as a basis for future research on computer-aided conceptual design.
According to the evolution of functional solving models, this paper first compares the characteristics and the consistency of the thinking process of three different functional solving models, including the extended function-environment-behaviour-structure (FEBS/e) model, the extended behaviour-driven function-environment-structure (B-FES/e) model, and the extended function-behaviour-implementation-environment (FBIE/e) model. Then, a new functional solving model with multiple elements and evolutions (FSMEE) is proposed. In this model, the reasoning process of product functional design is classified into 12 basic mapping relations by virtue of the regulation analysis of the design process. The evolutionary logic of basic mapping relations is then developed according to the optimal degree. In addition, the computer representation of the hierarchy design process is established by means of the topology relation matrices and adjacency relation matrices. Finally, an example of an emergency cut-off valve is presented to demonstrate the model's feasibility.
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