The causal relationship between gut microbiota and preterm birth: a two-sample Mendelian randomization study.

Background: Preterm birth, a significant global health concern, has been associated with alterations in the gut microbiota. However, the causal nature of this relationship remains uncertain due to the limitations inherent in observational studies.

Purpose: To investigate the potential causal relationship between gut microbiota imbalances and preterm birth.

Amuc_1100 pretreatment alleviates acute pancreatitis in a mouse model through regulating gut microbiota and inhibiting inflammatory infiltration.

Amuc_1100 is a membrane protein from Akkermansia muciniphila, which has been found to play a role in host immunological homeostasis in the gastrointestinal tract by activating TLR2 and TLR4. In this study we investigated the effects and underlying mechanisms of Amuc_1100 on acute pancreatitis (AP) induced in mice by intraperitoneal injection of caerulein and lipopolysaccharide (LPS). The mice were treated with the protein Amuc_1100 (3 μg, i.

Identification of a Potential Antimycobacterial Drug Sensitizer Targeting a Flavin-Independent Methylenetetrahydrofolate Reductase.

The increasing antibiotic resistance of and pathogenic nontuberculosis mycobacteria highlights the urgent need for new prevention and treatment strategies. Recently, the cocrystal structure of a flavin-independent 5,10-methylenetetrahydrofolate reductase (MTHFR) that binds with a reduced nicotinamide adenine dinucleotide (NADH) has been well-determined, providing a structural basis for the screening of antimycobacterial leads targeting MTHFR, a new enzyme involved in tetrahydrofolic acid (THF) biosynthesis. In this study, we identified compound AB131 as a promising candidate that fits well into the NADH binding pocket of MTHFR through virtual screening.

In vitro antifungal and antibiofilm activities of auranofin against itraconazole-resistant Aspergillus fumigatus.

Background: Infections caused by azole-resistant Aspergillus are a rising public health threat with high mortality rates, high treatment costs and limited available antifungals, indicating an urgent need for new antifungals or strategies. Our aim was to investigate antifungal and antibiofilm activities of auranofin, an FDA-approved anti-antirheumatic drug.

Methods: Fungal susceptibility testing for auranofin was carried out by the broth-based microdilution methods.

Investigations into the antibacterial effects and potential mechanism of gambogic acid and neogambogic acid.

The growing threat of antibiotic-resistant bacterial infections to public health necessitates the development of novel antibacterial agents. Inhibiting bacterial cell wall synthesis has remained a key focus for antibiotic development. Our search for inhibitors of undecaprenyl diphosphate synthase (UPPS), an essential enzyme required for bacterial cell wall formation, revealed that two primary components of gamboge, gambogic acid (GA) and neogambogic acid (NGA), significantly inhibited the activity of UPPS (UPPS) with the half maximal inhibitory concentrations (IC) of 3.

Structural basis of three different transcription activation strategies adopted by a single regulator SoxS.

Transcription activation is established through extensive protein-protein and protein-DNA interactions that allow an activator to engage and remodel RNA polymerase. SoxS, a global transcription activator, diversely regulates subsets of stress response genes with different promoters, but the detailed SoxS-dependent transcription initiation mechanisms remain obscure. Here, we report cryo-EM structures of three SoxS-dependent transcription activation complexes (SoxS-TACI, SoxS-TACII and SoxS-TACIII) comprising of Escherichia coli RNA polymerase (RNAP), SoxS protein and three representative classes of SoxS-regulated promoters.

Structural basis of transcription activation by Rob, a pleiotropic AraC/XylS family regulator.

Rob, which serves as a paradigm of the large AraC/XylS family transcription activators, regulates diverse subsets of genes involved in multidrug resistance and stress response. However, the underlying mechanism of how it engages bacterial RNA polymerase and promoter DNA to finely respond to environmental stimuli is still elusive. Here, we present two cryo-EM structures of Rob-dependent transcription activation complex (Rob-TAC) comprising of Escherichia coli RNA polymerase (RNAP), Rob-regulated promoter and Rob in alternative conformations.

Structural basis of transcription activation by the global regulator Spx.

Spx is a global transcriptional regulator in Gram-positive bacteria and has been inferred to efficiently activate transcription upon oxidative stress by engaging RNA polymerase (RNAP) and promoter DNA. However, the precise mechanism by which it interacts with RNAP and promoter DNA to initiate transcription remains obscure. Here, we report the cryo-EM structure of an intact Spx-dependent transcription activation complex (Spx-TAC) from Bacillus subtilis at 4.