Thiopeptide Antibiotics Exhibit a Dual Mode of Action against Intracellular Pathogens by Affecting Both Host and Microbe

SummaryThiostrepton (TSR) is an archetypal thiopeptide antibiotic possessing a quinaldic acid (QA) moiety in the side ring system. According to the mechanism of TSR previously known to target bacterial ribosome, we recently designed and biosynthesized several TSR derivatives that varied in QA substitution. Utilizing these thiopeptide antibiotics to treat the intracellular pathogen Mycobacterium marinum, we herein report a novel mode of action of TSRs, which induce ER stress-mediated autophagy to enhance host cell defense. This intracellular response, which is sensitive to the modification of the QA group, serves as an indirect but unignorable mechanism for eliminating intracellular pathogens. TSRs are thus the only type of antibiotics, to our knowledge, with the dual action on both the parasitic bacteria and the infected host cells. The newly observed mechanism of TSRs may inspire the future change in the treatment of intracellular pathogens, by taking host response into account

Evolution of Guangzhou Biomedical Industry Innovation Network Structure and Its Proximity Mechanism

The topological structure and multidimensional proximity evolution mechanism of Guangzhou biomedical industry innovation network are studied by using cooperative patents and cooperative papers from 1998 to 2018 with Ucinet and PLS-SEM. Research shows: ① The evolution of the Guangzhou Biomedical Industry Innovation Network can be divided into three stages, which are the primary budding stage of 1998–2005, the steady development stage of 2006–2012, and the rapid development stage of 2013–2018; ② the number of subjects in the innovation network is increasing, and the types of subjects are constantly increasing. The innovation network has gone from small to large, from closed to open, and from simple to complex. Patents and papers cooperation networks show different characteristics at various stages; ③ the relationship between geographical proximity, cognitive proximity, organizational proximity, and innovation network differs in stages. The interaction of proximity varies with the content of innovation cooperation. Based on this result, we have put forward policy recommendations for different innovative content

Evolution of Guangzhou biomedical industry innovation network structure and its proximity mechanism

The topological structure and multidimensional proximity evolution mechanism of Guangzhou biomedical industry innovation network are studied by using cooperative patents and cooperative papers from 1998 to 2018 with Ucinet and PLS-SEM. Research shows: O1 The evolution of the Guangzhou Biomedical Industry Innovation Network can be divided into three stages, which are the primary budding stage of 1998–2005, the steady development stage of 2006–2012, and the rapid development stage of 2013–2018; O2 the number of subjects in the innovation network is increasing, and the types of subjects are constantly increasing. The innovation network has gone from small to large, from closed to open, and from simple to complex. Patents and papers cooperation networks show different characteristics at various stages; O3 the relationship between geographical proximity, cognitive proximity, organizational proximity, and innovation network differs in stages. The interaction of proximity varies with the content of innovation cooperation. Based on this result, we have put forward policy recommendations for different innovative content

Empirical Evaluation of the Impact of Informal Communication Space Quality on Innovation in Innovation Districts

Innovation and creativity have become the driving force of a new round of urban development. Innovation districts have increasingly attracted the attention of domestic and foreign governments and scholars. An informal communication space is the main place for knowledge spillover, innovation communication, and transmission in innovation districts, and its spatial quality plays a vital role in the cultivation and development of innovation districts. The existing quality evaluation of informal communication spaces is less innovative. Based on the perspective of innovation, this paper selects the spatial characteristics of parks, squares, and pedestrian streets from three dimensions of morphology, function, and image, and establishes a preliminary evaluation index system. On the other hand, this paper combs the influence theory of knowledge spillover on innovation and summarizes the communication atmosphere, communication frequency, communication object and communication quality as the dependent variables of innovation. Through correlation analysis and multiple linear regression analysis, innovative informal communication space features are screened out, and the spatial quality evaluation index systems of parks, squares, and pedestrian streets are constructed, respectively. In the empirical study, 24 samples of Gaoxin South District (GXSD) are selected for spatial quality evaluation. Subjective evaluation and objective evaluation are used to obtain the advantages and disadvantages of different spaces to stimulate innovation. This study is helpful for urban designers and planners to better carry out space design to promote innovation through evaluating space status