Identification of biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in alcoholic hepatitis by bioinformatics and experimental verification

BackgroundsAlcoholic hepatitis (AH) is a major health problem worldwide. There is increasing evidence that immune cells, iron metabolism and copper metabolism play important roles in the development of AH. We aimed to explore biomarkers that are co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients.MethodsGSE28619 and GSE103580 datasets were integrated, CIBERSORT algorithm was used to analyze the infiltration of 22 types of immune cells and GSVA algorithm was used to calculate ferroptosis and cuproptosis scores. Using the “WGCNA” R package, we established a gene co-expression network and analyzed the correlation between M1 macrophages, ferroptosis and cuproptosis scores and module characteristic genes. Subsequently, candidate genes were screened by WGCNA and differential expression gene analysis. The LASSO-SVM analysis was used to identify biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis. Finally, we validated these potential biomarkers using GEO datasets (GSE155907, GSE142530 and GSE97234) and a mouse model of AH.ResultsThe infiltration level of M1 macrophages was significantly increased in AH patients. Ferroptosis and cuproptosis scores were also increased in AH patients. In addition, M1 macrophages, ferroptosis and cuproptosis were positively correlated with each other. Combining bioinformatics analysis with a mouse model of AH, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 may be potential biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients.ConclusionWe identified 5 potential biomarkers that are promising new targets for the treatment and diagnosis of AH patients

Hippo signalling governs cytosolic nucleic acid sensing through YAP/TAZ-mediated TBK1 blockade

The Hippo pathway senses cellular conditions and regulates YAP/TAZ to control cellular and tissue homeostasis, while TBK1 is central for cytosolic nucleic acid sensing and antiviral defence. The correlation between cellular nutrient/physical status and host antiviral defence is interesting but not well understood. Here we find that YAP/TAZ act as natural inhibitors of TBK1 and are vital for antiviral physiology. Independent of transcriptional regulation and through the transactivation domain, YAP/TAZ associate directly with TBK1 and abolish virus-induced TBK1 activation, by preventing TBK1 Lys63-linked ubiquitylation and the binding of adaptors/substrates. Accordingly, YAP/TAZ deletion/depletion or cellular conditions inactivating YAP/TAZ through Lats1/2 kinases relieve TBK1 suppression and boost antiviral responses, whereas expression of the transcriptionally inactive YAP dampens cytosolic RNA/DNA sensing and weakens the antiviral defence in cells and zebrafish. Thus, we describe a function of YAP/TAZ and the Hippo pathway in innate immunity, by linking cellular nutrient/physical status to antiviral host defence

Identification of the original species of cubilose based on DNA barcode

Cubilose, a valuable traditional Chinese medicine, is mainly composed of the saliva by several species of Aerodramus or Collocalia in the Apodidae. Due to rarity, high economic value and huge market demand, its fake or adulteration is frequently found in the market. Therefore, it is urgent to establish a simple and accurate method for authenticating cubilose. DNA barcoding, which is an easy, quick and reliable method, is widely used to trace the origin of traditional Chinese medicine. For identifying the original species of cubilose, cytb gene of 18 cubilose samples including 15 officer cubilose and 3 feather cubilose were amplified and entered into the GenBank database using the BLAST search tool. The genetic distances among 18 cubilose samples were calculated based on the Kimura two parameter (K2P) model. To construct the reference database, 18 cytb sequences of Aerodramus or Collocalia were downloaded from GenBank. The neighbor-joining (NJ) and unweighted pair group method with arithmetic average (UPGMA) trees were constructed based on sequences from GenBank and our dataset. Blast analysis showed that all cubilose samples had the highest similarity with A. fuciphagus, and the sequence similarity reached over 99%. Genetic distance of 18 cubilose samples ranged from 0.000–0.010. Trees constructed by NJ and UPGMA gave similar topology: all cubilose samples clustered together with A. fuciphagus. These result demonstrated that the original species of all 18 cubilose samples were A. fuciphagus, and cytb gene is a good candidate for identifying cubilose

Feasibility of Replacing the Range Doppler Equation of Spaceborne Synthetic Aperture Radar Considering Atmospheric Propagation Delay with a Rational Polynomial Coefficient Model

Usually, the rational polynomial coefficient (RPC) model of spaceborne synthetic aperture radar (SAR) is fitted by the original range Doppler (RD) model. However, the radar signal is affected by two-way atmospheric delay, which causes measurement error in the slant range term of the RD model. In this paper, two atmospheric delay correction methods are proposed for use in terrain-independent RPC fitting: single-scene SAR imaging with a unique atmospheric delay correction parameter (plan 1) and single-scene SAR imaging with spatially varying atmospheric delay correction parameters (plan 2). The feasibility of the two methods was verified by conducting fitting experiments and geometric positioning accuracy verification of the RPC model. The experiments for the GF-3 satellite were performed by using global meteorological data, a global digital elevation model, and ground control data from several regions in China. The experimental results show that it is feasible to use plan 1 or plan 2 to correct the atmospheric delay error, no matter whether in plain, mountainous, or plateau areas. Moreover, the geometric positioning accuracy of the RPC model after correcting the atmospheric delay was improved to better than 3 m. This is of great significance for the efficient and high-precision geometric processing of spaceborne SAR images

Opportunistic-tended life history traits of Siniperca kneri in the Three Gorges Reservoir, China: potential responses to impoundment

Reservoir impoundment changes original fluvial habitats into lentic environments. Fish species adapted to lentic habitats may take the advantage of such habitat changes and show typical life history traits might facilitate the population increase. Siniperca kneri rarely occurred in fishery landing in the Three Gorges Reservoir (TGR) area before its impoundment in 2003, but it is now a dominant species. In this study, a total of 438 females of S. kneri were collected monthly during September 2012 through January 2014 using gill nets in the TGR. The age, growth, and reproductive biology were then investigated, and compared with other S. kneri populations. The standard length at age 1 was 149.9 mm in the TGR, which is larger than the three compared populations (i.e., Sandaohe Reservoir, Xinfengjiang Reservoir, and North River), but smaller than one (the Guishi Reservoir). The youngest mature female in the TGR was age 1, which is younger than that of the two compared populations (i.e., Xinfengjiang Reservoir and the North River). The relative fecundity in the TGR was 140 eggs/g, which is higher than that of the only available compared population (Xinfengjiang Reservoir, 96 eggs/g). Our results demonstrated that S. kneri in the TGR tended to have faster growth in the first year, a younger age at first maturation, and higher reproductive effort. We suggest that such opportunistic-tended life history traits might facilitate rapid increase of the population.</p

Shifting chemical defence or novel weapons? A review of defence traits in Agarophyton vermiculophyllum and other invasive seaweeds

Seaweed bioinvasions increasingly affect coastal environments around the world, which increases the need for predictive models and mitigation strategies. The biotic interactions between seaweed invaders and invaded communities are often considered a key determinant of invasion success and failure and we here revise the current evidence that the capacity of seaweed invaders to deter enemies in newly reached environments correlates with their invasion success. Particularly efficient chemical defences have been described for several of the more problematic seaweed invaders during the last decades. However, confirmed cases in which seaweed invaders confronted un-adapted enemies in newly gained environments with deterrents that were absent from these environments prior to the invasion (so-called “novel weapons”) are scarce, although an increasing number of invasive and non-invasive seaweeds are screened for defence compounds. More evidence exists that seaweeds may adapt defence intensities to changing pressure by biological enemies in newly invaded habitats. However, most of this evidence of shifting defence was gathered with only one particular model seaweed, the Asia-endemic red alga Agarophyton vermiculophyllum, which is particularly accessible for direct comparisons of native and non-native populations in common garden experiments. A. vermiculophyllum interacts with consumers, epibionts and bacterial pathogens and in most of these interactions, non-native populations have rather gained than lost defensive capacity relative to native conspecifics. The increases in the few examined cases were due to an increased production of broad-spectrum deterrents and the relative scarcity of specialized deterrents perhaps reflects the circumstance that seaweed consumers and epibionts are overwhelmingly generalists