Microbiome-derived bile acids contribute to elevated antigenic response and bone erosion in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, disabling and incurable autoimmune disease. It has been widely recognized that gut microbial dysbiosis is an important contributor to the pathogenesis of RA, although distinct alterations in microbiota have been associated with this disease. Yet, the metabolites that mediate the impacts of the gut microbiome on RA are less well understood. Here, with microbial profiling and non-targeted metabolomics, we revealed profound yet diverse perturbation of the gut microbiome and metabolome in RA patients in a discovery set. In the Bacteroides-dominated RA patients, differentiation of gut microbiome resulted in distinct bile acid profiles compared to healthy subjects. Predominated Bacteroides species expressing BSH and 7a-HSDH increased, leading to elevated secondary bile acid production in this subgroup of RA patients. Reduced serum fibroblast growth factor-19 and dysregulated bile acids were evidence of impaired farnesoid X receptor-mediated signaling in the patients. This gut microbiota-bile acid axis was correlated to ACPA. The patients from the validation sets demonstrated that ACPA-positive patients have more abundant bacteria expressing BSH and 7a-HSDH but less Clostridium scindens expressing 7a-dehydroxylation enzymes, together with dysregulated microbial bile acid metabolism and more severe bone erosion than ACPA-negative ones. Mediation analyses revealed putative causal relationships between the gut microbiome, bile acids, and ACPA-positive RA, supporting a potential causal effect of Bacteroides species in increasing levels of ACPA and bone erosion mediated via disturbing bile acid metabolism. These results provide insights into the role of gut dysbiosis in RA in a manifestation-specific manner, as well as the functions of bile acids in this gut-joint axis, which may be a potential intervention target for precisely controlling RA conditions.Comment: 38 pages, 6 figure

High Purity and Low Molecular Weight Lignin Nano-Particles Extracted from Acid-Assisted MIBK Pretreatment

A simple and economical biorefinery method, organosolv methyl isobutyl ketone (MIBK) pretreatment assisted by Lewis acid ferric trichloride hydrolysis, was proposed for fractionating the lignin from extractive-free Eucalyptus powder at the nanoscale, accompanied by another product furfural, derived from hemicellulose. Under the conditions (180 °C, 1 h) optimized based on the best yield of furfural, 40.13% of the acid-insoluble lignin (AIL) could be obtained with a high purity of 100%, a low molecular weight of 767 (Mn) and improved thermostability. The extracted lignin was characterized by its chemical structure, thermostability, homogeneity, molecular weight, and morphology as compared with milled wood lignin (MWL). The results showed significant variations in chemical structures of the extracted lignin during the pretreatment. Specifically, the aryl ether linkage and phenylcoumarans were broken severely while the resinols were more resistant. The G-type lignin was more sensitive to degradation than the S-type, and after the pretreatment, H-type lignin was formed, indicating the occurrence of a demethoxylation reaction at high temperature. Moreover, the lignin nano-particles were identified visually by AFM and TEM images. The dynamic light scattering (DLS) showed that the average diameter of the measured samples was 131.8 nm, with the polydispersity index (PDI) of 0.149. The MIBK-lignin nano-particles prepared in our laboratory exhibit high potentials in producing high functional and valuable materials for the application in wide fields

Glibenclamide pretreatment attenuates early hematoma expansion of warfarin-associated intracerebral hemorrhage in rats by alleviating perihematomal blood–brain barrier dysfunction

Abstract Background Hematoma expansion is a determinant of poor outcome of intracerebral hemorrhage but occurs frequently, especially in warfarin-associated intracerebral hemorrhage (W-ICH). In the present study, we employ the warfarin-associated intracerebral hemorrhage (W-ICH) rat model, to explore the efficacy and potential mechanism of glibenclamide pretreatment on hematoma expansion after intracerebral hemorrhage, hoping to provide proof of concept that glibenclamide in stroke primary and secondary prevention is also potentially beneficial for intracerebral hemorrhage patients at early stage. Methods In the present study, we tested whether glibenclamide, a common hypoglycemic drug, could attenuate hematoma expansion in a rat model of W-ICH. Hematoma expansion was evaluated using magnetic resonance imaging; brain injury was evaluated by brain edema and neuronal death; and functional outcome was evaluated by neurological scores. Then blood–brain barrier integrity was assessed using Evans blue extravasation and tight junction-related protein. Results The data indicated that glibenclamide pretreatment significantly attenuated hematoma expansion at 24 h after W-ICH, thus mitigating brain edema and neuronal death and promoting neurological function recovery, which may benefit from alleviating blood–brain barrier disruption by suppressing matrix metallopeptidase-9. Conclusions The results indicate that glibenclamide pretreatment in stroke primary and secondary prevention might be a promising therapy for hematoma expansion at the early stage of W-ICH

Development Trend of Electronic Nose Technology in Closed Cabins Gas Detection: A Review

Gas detection in enclosed cabins is a challenging concern in the industry to ensure the safety of cabin operations and personnel driving. There has been a growing development in the detection of safety in enclosed cabin operations based on volatile organic compounds, which have unique characteristics. The air pollution in closed cabins seriously affects the driver’s health, and the accuracy of the detection directly affects the operation safety of the cabin. However, until today, gas detection in enclosed cabins has relied on traditional methods that are expensive and time-consuming, and it cannot be detected in real time. This paper focuses on the potential and capability of electronic nose applications for gas detection in enclosed cabins. Since the electronic nose is a good substitute for the closed cabin, people’s attention to it has increased greatly. The characteristics of hazardous gas and warning gas in closed cabins are also discussed. In addition, this paper provides important insights into the challenges and future trends of the electronic nose, a low-cost, high-precision, and fast detection method, in more applications in closed compartments