Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.
Nanogenerators capable of converting energy from mechanical sources to electricity with high effective efficiency using low-cost, nonsemiconducting, organic nanomaterials are attractive for many applications, including energy harvesters. In this work, near-field electrospinning is used to direct-write poly(vinylidene fluoride) (PVDF) nanofibers with in situ mechanical stretch and electrical poling characteristics to produce piezoelectric properties. Under mechanical stretching, nanogenerators have shown repeatable and consistent electrical outputs with energy conversion efficiency an order of magnitude higher than those made of PVDF thin films. The early onset of the nonlinear domain wall motions behavior has been identified as one mechanism responsible for the apparent high piezoelectricity in nanofibers, rendering them potentially advantageous for sensing and actuation applications.
A universal but simple procedure for identifying the α, β and γ phases in PVDF using FTIR is proposed and validated. An integrated quantification methodology for individual β and γ phase in mixed systems is also proposed.
Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA), a molecular signature of most viruses, and triggers inflammatory responses that prevent viral spread. TLR3 ectodomains (ECDs) dimerize on oligonucleotides of at least 40 to 50 base pairs in length, the minimal length required for signal transduction. To establish the molecular basis for ligand binding and signaling, we determined the crystal structure of a complex between two mouse TLR3-ECDs and dsRNA at 3.4 angstrom resolution. Each TLR3-ECD binds dsRNA at two sites located at opposite ends of the TLR3 horseshoe, and an intermolecular contact between the two TLR3-ECD C-terminal domains coordinates and stabilizes the dimer. This juxtaposition could mediate downstream signaling by dimerizing the cytoplasmic Toll interleukin-1 receptor (TIR) domains. The overall shape of the TLR3-ECD does not change upon binding to dsRNA.
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