Invasiveness of the Yersinia pestis ail protein contributes to host dissemination in pneumonic and oral plague

Yersinia pestis, a Gram-negative bacterium, is the etiologic agent of plague. A hallmark of Y. pestis infection is the organism's ability to rapidly disseminate through an animal host. Y. pestis expresses the outer membrane protein, Ail (Attachment invasion locus), which is associated with host invasion and serum resistance. However, whether Ail plays a role in host dissemination remains unclear. In this study, C57BL/6J mice were challenged with a defined Y. pestis strain, KimD27, or an isogenic ail-deleted mutant derived from KimD27 via metacarpal paw pad inoculation, nasal drops, orogastric infection, or tail vein injection to mimic bubonic, pneumonic, oral, or septicemic plague, respectively. Our results showed that ail-deleted Y. pestis KimD27 lost the ability to invade host cells, leading to failed host dissemination in the pneumonic and oral plague models but not in the bubonic or septicemic plague models, which do not require invasiveness. Therefore, this study demonstrated that whether Ail plays a role in Y. pestis pathogenesis depends on the infection route.Peer reviewe

Oral vinorelbine and continuous low doses of cyclophosphamide in pediatric rhabdomyosarcoma: a real-world study

Introduction: Metronomic maintenance therapy (MMT) has significantly improved the survival of patients with high-risk rhabdomyosarcoma in clinical trials. However, there remains a lack of relevant data on its effectiveness in real-world situations.Methods: We retrospectively retrieved data of 459 patients < 18 years of age diagnosed with rhabdomyosarcoma at Sun Yat-sen University Cancer Center from January 2011 to July 2020 from our database. The MMT regimen was oral vinorelbine 25–40 mg/m2 for twelve 4-week cycles on days 1, 8, and 15, and oral cyclophosphamide 25–50 mg/m2 daily for 48 consecutive weeks.Results: A total of 57 patients who underwent MMT were included in the analysis. The median follow-up time was 27.8 (range: 2.9–117.5) months. From MMT to the end of follow-up, the 3-year PFS and OS rates were 40.6% ± 6.8% and 58.3% ± 7.2%, respectively. The 3-year PFS was 43.6% ± 11.3% in patients who were initially diagnosed as low- and intermediate-risk but relapsed after comprehensive treatment (20/57), compared with 27.8% ± 10.4% in high-risk patients (20/57) and 52.8% ± 13.3% in intermediate-risk patients who did not relapse (17/57). The corresponding 3-year OS for these three groups was 65.8% ± 11.4%, 50.1% ± 12.9%, and 55.6% ± 13.6%, respectively.Conclusion: We present a novel study of MMT with oral vinorelbine and continuous low doses of cyclophosphamide in real-world pediatric patients with RMS. Our findings showed that the MMT strategy significantly improved patient outcomes and may be an effective treatment for high-risk and relapsed patients

Antimicrobial peptide temporin derivatives inhibit biofilm formation and virulence factor expression of Streptococcus mutans

IntroductionTemporin-GHa obtained from the frog Hylarana guentheri showed bactericidal efficacy against Streptococcus mutans. To enhance its antibacterial activity, the derived peptides GHaR and GHa11R were designed, and their antibacterial performance, antibiofilm efficacy and potential in the inhibition of dental caries were evaluated.MethodsBacterial survival assay, fluorescent staining assay and transmission electron microscopy observation were applied to explore how the peptides inhibited and killed S. mutans. The antibiofilm efficacy was assayed by examining exopolysaccharide (EPS) and lactic acid production, bacterial adhesion and cell surface hydrophobicity. The gene expression level of virulence factors of S. mutans was detected by qRT-PCR. Finally, the impact of the peptides on the caries induced ability of S. mutans was measured using a rat caries model.ResultsIt has been shown that the peptides inhibited biofilm rapid accumulation by weakening the initial adhesion of S. mutans and reducing the production of EPS. Meanwhile, they also decreased bacterial acidogenicity and aciduricity, and ultimately prevented caries development in vivo.ConclusionGHaR and GHa11R might be promising candidates for controlling S. mutans infections

PgtE Enzyme of Salmonella enterica Shares the Similar Biological Roles to Plasminogen Activator (Pla) in Interacting With DEC-205 (CD205), and Enhancing Host Dissemination and Infectivity by Yersinia pestis

Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.Peer reviewe

Energy saving potential of fragmented green spaces due to their temperature regulating ecosystem services in the summer

Urban green spaces help to moderate the urban heat island (UHI) effects, and can provide important temperature regulating ecosystem services and opportunities for savings in cooling energy. However, because explicit market values for these benefits are still lacking, they are rarely incorporated into urban planning actions. Green spaces can generate a three-dimensional (3D) cool island that may reduce the cooling energy requirements within and around urban areas, but such 3D cooling effect has not been considered in previous studies quantifying energy savings from green spaces. This study presents a new and simple approach to quantify potential energy savings due to the temperature regulating ecosystem services of small-scale fragmented green spaces using the 3D simulation of the summer-day outdoor thermal environment in Nanjing, China. Field survey data and the microclimate model ENVI-met were applied to examine the outdoor 3D thermal environmental patterns at Gulou Campus of Nanjing University under two different scenarios: “with” and “without” green spaces. Modeling results were applied to quantify potential cooling energy savings based on the effect of green spaces on the outdoor urban environment and to calculate the cumulative temperature reduction due to green spaces using a regression model. The results show that, in the horizontal direction, the simulated distribution of wind speed and mean air temperature at 1.5 m height were closely related to the spatial distribution of the underlying surface types. Removal of green spaces increased mean air temperature by 0.5 °C (33.1 °C vs. 33.6 °C). In the vertical direction, removal of green spaces had little effect on the near-surface wind field; however, above the surface, the turbulence perpendicular to the main wind direction significantly increased. Quantification of the cooling benefits of green spaces in relation to the mean height of buildings on Gulou Campus yielded 5.2 W/m2 cooling energy, saving totally 1.3 × 104 kW h during a single daytime hot summer period. This case study corroborates the importance of green space for cooling and informs city planners and decision-makers on how microclimate is impacted by the loss of green spaces. These findings will facilitate preservation, planning, and design of green spaces to increase urban environmental benefits and to improve the microclimate of urban areas at neighborhood, city, and regional scales

The complete chloroplast genome sequence of Michelia macclurei (Dandy, 1928) (Magnoliaceae), an important fire-resistant tree species

Michelia macclurei (Dandy, 1928) is an evergreen broad-leaved tree species native to South China. This species has great ecological and economic importance. However, the genomic study of M. macclurei has lagged far behind. Here, we reported the complete chloroplast genome sequence of M. macclurei. The chloroplast genome size of M. macclurei was 160,139 bp, consisting of a pair of inverted repeat (IR) regions (26,575 bp), which was separated by a large single copy (LSC) region (88,167 bp) and a small single copy (SSC) region (18,822 bp). A total of 113 unique genes were annotated, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The overall GC content was 39.2%. Phylogenetic analysis based on 16 whole chloroplast genome sequences of Michelia species suggested that M. macclurei and M. maudiae are sister to each other, and jointly sister to M. chapensis

From Offline Towards Real-Time Verification for Robot Systems

Robot systems have been widely used in industry and also play an important role in human social life. Safety critical applications usually demand rigorously formal verification to ensure correctness. But for the increasing complexity of dynamic environments and applications, it is not easy to build a comprehensive model for the traditional offline verification. In this paper, we propose RobotRV, the first data-centered real-time verification approach for the robot system. Within this approach, a domain-specific language named RoboticSpec is designed to specify the complex application scenario of the robot system, the data packets transmitted in the robot system, and the safety critical temporal properties. Then, we develop an engine to automatically translate the RoboticSpec model into a real-time verifier. The generated verifier serves as an independent plug-in component for the runtime verification of concerned temporal properties. We applied the proposed approach to a real robot system. As presented in experiment results, our method detected potential failures, and improved the safety of robot system

From Offline Towards Real-Time Verification for Robot Systems

Robot systems have been widely used in industry and also play an important role in human social life. Safety critical applications usually demand rigorously formal verification to ensure correctness. But for the increasing complexity of dynamic environments and applications, it is not easy to build a comprehensive model for the traditional offline verification. In this paper, we propose RobotRV, the first data-centered real-time verification approach for the robot system. Within this approach, a domain-specific language named RoboticSpec is designed to specify the complex application scenario of the robot system, the data packets transmitted in the robot system, and the safety critical temporal properties. Then, we develop an engine to automatically translate the RoboticSpec model into a real-time verifier. The generated verifier serves as an independent plug-in component for the runtime verification of concerned temporal properties. We applied the proposed approach to a real robot system. As presented in experiment results, our method detected potential failures, and improved the safety of robot system

Analysis of Private Investors Conduct Strategies by Governments Supervising Public-Private Partnership Projects in the New Media Era

Private investors and governments need to cooperate in public–private partnership (PPP) projects but the private investors may be in pursuit of their own profit by conducting defaulting behaviors which causes various environmental problems and economic risks. However, the information asymmetry between them makes it difficult to supervise the behaviors of private investors. The development of internet and social media creates new environment for the information spread and people are using new media increasingly in the current society, providing an inexpensive and viable way for the public to participate in PPP projects. We constructed a dynamic evolutionary model to analyze the behaviors strategies of governments and private investors in the new media era and then analyzed how important factors influence the behavior trends of governments and private investors. These findings could provide meaningful insight to improve supervision status by using the new media environment and predict the behaviors of governments and private investors in PPP projects, which would be conductive for the governments to supervise the private investors in PPP projects more efficiently