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Multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) family transporters are essential in glycan synthesis, flipping lipid-linked precursors across cell membranes. Yet, how they select their substrates remains enigmatic. Here, we investigate the substrate specificity of the MOP transporters in the capsular polysaccharide (CPS) synthesis pathway in . These capsule flippases collectively transport more than 100 types of capsule precursors. To determine whether they can substitute for one another, we developed a high-throughput approach to systematically examine nearly 6000 combinations of flippases and substrates. CPS flippases fall into three groups: relaxed, type-specific, and strictly specific. Cargo size and CPS acetylation affect transport, and we isolated additional gain-of-function flippase variants that can substitute for the peptidoglycan flippase YtgP (MurJ). We also showed that combining flippase variants in a single cassette allows various CPS precursors to be flipped, which may aid glycoengineering. This study reveals that MOP flippases exhibit broad specificity, shaping the evolution of glycan synthesis.
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http://dx.doi.org/10.1126/sciadv.adr0162 | DOI Listing |
Arch Microbiol
September 2025
School of Public Health, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Wenjiang District, Chengdu, 611137, Sichuan Province, China.
The inhibitory effects of Lactiplantibacillus plantarum on inflammatory responses are known, but its action mechanisms in oxidative stress, immunomodulation, and intestinal homeostasis remain of interest. Accordingly, we investigated the protective effects of Lactiplantibacillus plantarum SCS2 (L. plantarum SCS2) against sodium dextran sulfate (DSS)-induced colitis in mice as well as elucidated its impact on inflammation, oxidative stress, and intestinal microbiota.
View Article and Find Full Text PDFElife
September 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Innate immune cells can acquire a memory phenotype, termed trained immunity, but the mechanism underlying the regulation of trained immunity remains largely elusive. Here, we demonstrate that inhibition of Aurora kinase A (AurA) dampens trained immunity induced by β-glucan. ATAC-seq and RNA-seq analysis reveal that AurA inhibition restricts chromatin accessibility of genes associated with inflammatory pathways such as JAK-STAT, TNF, and NF-κB pathways.
View Article and Find Full Text PDFInt J Vitam Nutr Res
September 2025
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, 300070 Tianjin, China.
Background: Retinol-binding protein 4 (RBP4) is a vitamin A transport protein synthesized in the liver and also plays a crucial role in inflammation and immune regulation. Low serum vitamin A levels have been observed in both pediatric and adult patients with ulcerative colitis (UC). The association between serum vitamin A levels and serum RBP4 levels, as well as the underlying mechanism involved inimpaired vitamin A transport during inflammation in UC patients, has yet to been investigated.
View Article and Find Full Text PDFInt J Nanomedicine
September 2025
School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, 450001, People's Republic of China.
Purpose: This study aimed to develop a composite nanozyme system (Au/PB-Ce6-HA) based on gold nanoparticles (AuNPs) and Prussian blue nanoparticles (PBNPs) to combat tumor hypoxia and insufficient endogenous hydrogen peroxide (HO) deficiency, thus enhancing the efficacy of sonodynamic therapy (SDT) and starvation therapy for liver cancer.
Methods: The Au/PB-Ce6-HA system was constructed by in situ embedding AuNPs on PBNPs, loading the sonosensitizer Chlorin e6 (Ce6), and surface-coating with thiolated hyaluronic acid (HA-SH). The system was evaluated both in vitro and in vivo to assess its ability to catalyze glucose to generate HO, decompose HO to produce oxygen, and generate highly toxic reactive oxygen species (ROS) under ultrasound irradiation.
Front Immunol
September 2025
Department of Pediatric Nephrology, Radboud University Medical Centre, Amalia Children's Hospital, Nijmegen, Netherlands.
Hemolytic uremic syndrome caused by an invasive infection (SP-HUS) is a rare and severe disease that primarily affects children under two years of age. The pathophysiology of SP-HUS remains poorly understood, and treatment is largely supportive. Complement factor H (FH) is a key regulator of the alternative pathway of the complement system.
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