Burkholderia cenocepacia integrates cis-2-dodecenoic acid and cyclic dimeric guanosine monophosphate signals to control virulence.

Quorum sensing (QS) signals are used by bacteria to regulate biological functions in response to cell population densities. Cyclic diguanosine monophosphate (c-di-GMP) regulates cell functions in response to diverse environmental chemical and physical signals that bacteria perceive. In Burkholderia cenocepacia, the QS signal receptor RpfR degrades intracellular c-di-GMP when it senses the QS signal cis-2-dodecenoic acid, also called Burkholderia diffusible signal factor (BDSF), as a proxy for high cell density. However, it was unclear how this resulted in control of BDSF-regulated phenotypes. Here, we found that RpfR forms a complex with a regulator named GtrR (BCAL1536) to enhance its binding to target gene promoters under circumstances where the BDSF signal binds to RpfR to stimulate its c-di-GMP phosphodiesterase activity. In the absence of BDSF, c-di-GMP binds to the RpfR-GtrR complex and inhibits its ability to control gene expression. Mutations in rpfR and gtrR had overlapping effects on both the B. cenocepacia transcriptome and BDSF-regulated phenotypes, including motility, biofilm formation, and virulence. These results show that RpfR is a QS signal receptor that also functions as a c-di-GMP sensor. This protein thus allows B. cenocepacia to integrate information about its physical and chemical surroundings as well as its population density to control diverse biological functions including virulence. This type of QS system appears to be widely distributed in beta and gamma proteobacteria.

Quality assessment and its influencing factors of lung cancer clinical research registration: a cross-sectional analysis.

Background: A better understanding of the current features of lung cancer clinical research registration is important for improving registration quality and standardizing the registration. This study aimed to assess the registration quality of lung cancer studies on ClinicalTrials.gov and analyze the influencing factors. Methods: Lung cancer clinical researches registered in the ClinicalTrials.gov database were searched on 7 July 2021. The characteristics of trials that registered up to 7 July 2021 were assessed. The quality of completed and terminated lung cancer studies from 1 July 2007 to 7 July 2020 was assessed using a modified version of the World Health Organization (WHO) Trial Registration Data Set (TRDS, V.1.3.1). Multivariate logistic regression analysis was also used to analyze the factors influencing study registration quality. An above-average registration quality score represented a high registration quality. Results: A total of 6,448 clinical studies on lung cancer were used to summarise the registration characteristics. Most interventional studies were randomized (41.88%), single group (48.07%), and open-label (82.86%) studies, while most observational studies were cohort studies (59.08%). In total, 2,171 completed and terminated studies were assessed, with an average quality score (out of 54) of 36.76±5.69. None of the assessed studies had a 100% modified TRDS reporting rate, and missing summary results were the main factor affecting the quality scores. Multivariate logistic regression analyses showed that prospective registrations [adjusted odds ratio (aOR), 2.18; 95% confidence interval (CI), 1.79-2.65], multi-center studies (aOR, 1.73; 95% CI, 1.39-2.16), government-sponsored studies (aOR, 3.09; 95% CI, 1.48-6.42), and published studies (aOR, 1.43; 95% CI, 1.15-1.78) were more likely to be high quality research. Conclusions: To improve the quality of registration, awareness of prospective registration should be further improved and government investment should be increased. At the same time, more efficient and extensive data sharing after completion of the studies should be actively promoted.