Kuhuang alleviates liver fibrosis by modulating gut microbiota-mediated hepatic IFN signaling and bile acid synthesis

Background: Liver fibrosis is a common outcome of the pathological progression of chronic liver disease; however, no specific and effective therapeutic agent has been approved for its treatment. We investigated the effects of Kuhuang on liver fibrosis and the underlying mechanisms of action.Materials and methods: To induce hepatic fibrosis, either 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) diet was administered, or bile duct ligation (BDL) surgery was performed on C57BL/6 mice. Kuhuang was orally administered to mice for 7 days before and after bile duct ligation or 4 weeks with a DDC diet. Hematoxylin and eosin, Sirius red staining, and immunohistochemical analyses were performed to evaluate hepatic pathology. Hepatic interferon-β (IFN-β) levels were measured using an enzyme-linked immunosorbent assay. RNA sequencing was performed to examine the gene expression profiles of liver tissues. The mRNA expression of inflammatory, profibrotic, and bile acid (BA)-related genes was further validated by qRT-PCR. A targeted metabolomics assay revealed the alteration of the hepatic bile acid (BA) composition. The composition of the gut microbiota was determined via 16S rRNA sequencing.Results: Treatment with Kuhuang attenuated liver fibrosis and reduced the inflammatory response in bile duct ligation and DDC mouse models. In addition, the hepatic IFN signaling pathway was activated following Kuhuang treatment. Kuhuang treatment also significantly decreased hepatic levels of both primary and secondary BAs. In addition, Kuhuang treatment altered gut microbiota composition, with an increased abundance of interferon-inducing Akkermansia and decreased abundance of bile salt hydrolase-producing Lactobacillus, Clostridium, and Bifidobacterium. Furthermore, the abundance of Akkermansia was positively correlated with the hepatic mRNA expression levels of Ifna4, Ifnb, and Isg15, whereas that of Lactobacillus, Clostridium-sensu-stricto-1, and Bifidobacterium was positively correlated with levels of bile acid synthesis-related genes.Conclusion: Our results suggest that Kuhuang plays a protective role during the progression of liver fibrosis, potentially by altering the composition of the gut microbiota, which consequently activates interferon signaling and inhibits bile acid synthesis in the liver

NDH‐1L with a truncated NdhM subunit is unstable under stress conditions in cyanobacteria

Abstract Cyanobacterial NdhM, an oxygenic photosynthesis‐specific NDH‐1 subunit, has been found to be essential for the formation of a large complex of NDH‐1 (NDH‐1L). The cryo‐electron microscopic (cryo‐EM) structure of NdhM from Thermosynechococcus elongatus showed that the N‐terminus of NdhM contains three β‐sheets, while two α‐helixes are present in the middle and C‐terminal part of NdhM. Here, we obtained a mutant of the unicellular cyanobacterium Synechocystis 6803 expressing a C‐terminal truncated NdhM subunit designated NdhMΔC. Accumulation and activity of NDH‐1 were not affected in NdhMΔC under normal growth conditions. However, the NDH‐1 complex with truncated NdhM is unstable under stress. Immunoblot analyses showed that the assembly process of the cyanobacterial NDH‐1L hydrophilic arm was not affected in the NdhMΔC mutant even under high temperature. Thus, our results indicate that NdhM can bind to the NDH‐1 complex without its C‐terminal α‐helix, but the interaction is weakened. NDH‐1L with truncated NdhM is more prone to dissociation, and this is particularly evident under stress conditions

Hydrogen production from the air

Green hydrogen produced by water splitting using renewable energy is the most promising energy carrier of the low-carbon economy. However, the geographic mismatch between renewables distribution and freshwater availability poses a significant challenge to its production. Here, we demonstrate a method of direct hydrogen production from the air, namely, in situ capture of freshwater from the atmosphere using hygroscopic electrolyte and electrolysis powered by solar or wind with a current density up to 574 mA cm(−2). A prototype of such has been established and operated for 12 consecutive days with a stable performance at a Faradaic efficiency around 95%. This so-called direct air electrolysis (DAE) module can work under a bone-dry environment with a relative humidity of 4%, overcoming water supply issues and producing green hydrogen sustainably with minimal impact to the environment. The DAE modules can be easily scaled to provide hydrogen to remote, (semi-) arid, and scattered areas

Study on Microstructure and Mechanical Properties of Low Cost Ti-Fe-B Alloy

Microstructure evolution and mechanical properties of low cost Ti-2Fe-0.1B alloy under different heat treatment were studied. Results indicated that two kinds of equiaxed microstructures with different characteristics were obtained in conventional and double annealing, and typical lamellar microstructure was obtained in β annealing. Tensile test results shown that as-received rolled alloy possess highest strength and plasticity simultaneously due to fine and entangled microstructure. Uniform equiaxed dimples were observed in microstructure, which revealed ductile fracture morphology. Key words: titanium alloy; microstructure; heat treatment; mechanical propertie

High-Temperature Deformation Behavior and Microstructural Characterization of Ti-35421 Titanium Alloy

A self-designed Ti-35421 (Ti-3Al-5Mo-4Cr-2Zr-1Fe wt%) titanium alloy is a new type of low-cost high strength titanium alloy. In order to understand the hot deformation behavior of Ti-35421 alloy, isothermal compression tests were carried out under a deformation temperature range of 750–930 °C with a strain rate range of 0.01–10 s−1 in this study. Electron backscatter diffraction (EBSD) was used to characterize the microstructure prior to and post hot deformation. The results show that the stress–strain curves have obvious yielding behavior at a high strain rate (>0.1 s−1). As the deformation temperature increases and the strain rate decreases, the α phase content gradually decreases in the α + β phase region. Meanwhile, spheroidization and precipitation of α phase are prone to occur in the α + β phase region. From the EBSD analysis, the volume fraction of recrystallized grains was very low, so dynamic recovery (DRV) is the dominant deformation mechanism of Ti-35421 alloy. In addition to DRV, Ti-35421 alloy is more likely to occur in continuous dynamic recrystallization (CDRX) than discontinuous dynamic recrystallization (DDRX)

Carbon molecular sieving membranes for butane isomer separation

Membrane-based separations of hydrocarbon isomers are major challenges for the petrochemical industry. Herein, high quality carbon molecular sieving membranes (CMSMs) were prepared on gamma-alumina substrates from pyrolysis of P84 polymer membranes. Targeting at butane isomer separations, we tailored the slit-like ultramicropores of CMSMs at angstrom level by rational manipulations of the pyrolysis temperature. The crack-free CMSMs were obtained at 600 degrees C with the narrow and uniform ultramicropores centered at 6.0 a. A clear molecular size/shape discrimination was achieved successfully and remarkable n-butane permeance (384 GPU) and n-butane/iso-butane separation factor (74) was observed, which transcends the upper limit of well-intergrown crystalline zeolite membranes. Fine-tuning of the membrane thickness at sub-micron level, the n-butane permeance and n-butane/iso-butane separation factor were further optimized, which shows a great potential for petrochemical separation

Tailoring self-lubricating, wear-resistance, anticorrosion and antifouling properties of Ti/(Cu, MoS2)-DLC coating in marine environment by controlling the content of Cu dopant

In this study, the Ti/(Cu, MoS2)-DLC coatings with various Cu contents were prepared on stainless steel substrates by RF/DC magnetron sputtering technique. The effects of Cu content on microstructure, mechanical, tribological, anticorrosion and antifouling properties of coating were systematically investigated. Results showed that the addition of Cu could modify the composited microstructure and enhance the multi-functional protection of Ti/(Cu, MoS2)-DLC coating. As the increase of Cu content, the surface roughness and sp(2)/sp(3) ratio of Ti/(Cu, MoS2)-DLC coating presented an uptrend. Meanwhile, the hardness and elastic modulus of coating gradually displayed a downtrend. Overall, the coating with 7.6 at.% Cu exhibited optimal multi-functional protective effects in marine environment, including self-lubrication, wear-resistance, anticorrosion and antifouling ability