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The host-microbiome axis has been implicated in promoting anti-inflammatory immune responses. Yet, the underlying molecular mechanisms of commensal-mediated IL-10 production by regulatory B cells (Bregs) are not fully elucidated. Here, we demonstrate that bacterial CpG motifs trigger the signaling downstream of TLR9 promoting IκB NS -mediated expression of Blimp-1, a transcription regulator of IL-10. Surprisingly, this effect was counteracted by the NF-κB transcription factor c-Rel. A functional screen for intestinal bacterial species identified the commensal Clostridium sporogenes, secreting high amounts of short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs), as an amplifier of IL-10 production by promoting sustained mTOR signaling in B cells. Consequently, enhanced Breg functionality was achieved by combining CpG with the SCFA butyrate or the BCFA isovalerate thereby synergizing TLR- and mTOR-mediated pathways. Collectively, Bregs required two bacterial signals (butyrate and CpG) to elicit their full suppressive capacity and ameliorate T cell-mediated intestinal inflammation. Our study has dissected the molecular pathways induced by bacterial factors, which might contribute not only to better understanding of host-microbiome interactions, but also to exploration of new strategies for improvement of anti-inflammatory cellular therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Emergency departments across the U.S. are more congested than ever, and there is a pressing need to create capacity by improving patient flow. The long turnaround time of imaging tests, such as computed tomography (CT) scans, are a major reason for delays in treatment and disposition. Over an eight-month pre-intervention period during which 10,063 CT scans were ordered in our emergency department, the average time from a CT order to the availability of the radiologist's final report was 5.9 hours (median=4.2 hours). We created a multi-disciplinary team of physicians, nurses, technicians, transporters, informaticians, and engineers to identify barriers and implement technical as well as human-factors solutions. In the corresponding eight-month period after the implementation of the intervention bundle, there was a 1.2 hour reduction in CT turnaround time, despite a 13.8% increase in the number of CT scans ordered (p<0.0001).