Interferon regulatory factor 7- (IRF7-) mediated immune response affects Newcastle disease virus replication in chicken embryo fibroblasts

Interferon regulatory factor 7 (IRF7) is essential for the induction of an antiviral response. Previous studies have shown that virus replication causes the activation or expression of Type I interferon (IFN) in cells, which further activates IFN-stimulated genes (ISGs) to retard virus growth. In this study, after infection of chicken embryo fibroblasts (CEFs) with the lentogenic Newcastle disease virus (NDV) strain LaSota or the velogenic NDV strain GM, the mRNA and protein levels of IRF7 showed a significant increase, and part of the IRF7 protein was translocated from the cytoplasm to the nucleus. In order to further explore the effect of IRF7-mediated innate immune response on the replication of NDV in CEFs, the mRNA levels of IFN-α, IFN-β and STAT1 were measured and the replication kinetics of NDV determined. The results showed that specific siRNA could inhibit the expression of IRF7 and limit the mRNA level of IFN-α, IFN-β and STAT1 and, accordingly, the replication kinetics of both NDVs were enhanced after the inhibition of IRF7. In conclusion, IRF7 is an important nuclear transcription factor for the induction of Type I IFNs during the antiviral response, which can affect the replication of NDV and spread to CEFs in the early phase of viral infection

Production and decay of K-shell hollow krypton in collisions with 52 - 197 MeV/u bare xenon ions

X-ray spectra of K-shell hollow krypton atoms produced in single collisions with 52 - 197 MeV/u Xe54+ ions are measured in a heavy-ion storage ring equipped with an internal gas-jet target. Energy shifts of the K{\alpha}_1,2^s, K{\alpha}_1,2^(h,s), and K\b{eta}_1,3^s transitions are obtained. Thus, the average number of the spectator L-vacancies presented during the x-ray emission is deduced. From the relative intensities of the K{\alpha}_1,2^s and K{\alpha}_1,2^(h,s) transitions, the ratio of K-shell hollow krypton to singly K-shell ionized atoms is determined to be 14 - 24%. In the considered collisions, the K-vacancies are mainly created by the direct ionization which cannot be calculated within the perturbation descriptions. The experimental results are compared with a relativistic coupled channel calculation performed within the independent particle approximation.Comment: 5 figures, 9 pages. Accepted by Physical Review

Impact of Cordyceps sinensis on coronary computed tomography angiography image quality and renal function in a beagle model of renal impairment

ObjectiveThis study aims to investigate the protective effects of Cordyceps sinensis against renal injury induced by low-dose contrast medium (CM) in coronary computed tomography angiography (CCTA) imaging, and to evaluate its efficacy using functional magnetic resonance imaging (fMRI).MethodsTwenty Beagle dogs with induced renal insufficiency were enrolled in the study and randomly assigned to one of four groups (n = 5 per group). Group A received Cordyceps sinensis for 1 week prior to undergoing heart rate-dependent personalized CM CCTA scanning; Group B received Cordyceps sinensis for 1 week followed by conventional dose CM CCTA scanning; Group C did not receive Cordyceps sinensis but underwent HR-dependent CM CCTA scanning; and Group D did not receive Cordyceps sinensis but underwent conventional dose CM CCTA scanning. Renal function was assessed using MRI before and after the intervention, with IVIM (Intravoxel Incoherent Motion) and BOLD (Blood Oxygen Level Dependent) imaging of the kidneys. Key parameters, including the pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), and R2*values, were quantified. Laboratory renal function markers were measured multiple times before and after the intervention, and their correlation with fMRI parameters was analyzed.ResultsCCTA imaging revealed that the CT values of the major coronary artery branches in all groups met the international diagnostic criteria for coronary arteries. No statistically significant differences in image quality were observed among the four groups (P > 0.05). In Groups A and D, significant changes were observed in renal function parameters, as well as in D, D*, f, and R2* values, both pre- and post-CCTA (P < 0.05). However, Groups B and C exhibited no significant changes pre- and post-CCTA (P > 0.05). A significant correlation was found between MRI parameters and laboratory renal function markers, with excellent inter- and intra-observer reproducibility, and high repeatability in the measurements.ConclusionHR-dependent personalized CM CCTA imaging did not compromise image quality. Administration of Cordyceps sinensis demonstrated a potential protective effect on renal function. The combination of IVIM and BOLD functional MRI offers a reliable, non-invasive approach to assess the protective effects of Cordyceps sinensis on renal injury induced by low-dose CCTA in Beagle dogs

Screening and validation of atherosclerosis PAN-apoptotic immune-related genes based on single-cell sequencing

BackgroundCarotid atherosclerosis (CAS) is a complication of atherosclerosis (AS). PAN-optosome is an inflammatory programmed cell death pathway event regulated by the PAN-optosome complex. CAS’s PAN-optosome-related genes (PORGs) have yet to be studied. Hence, screening the PAN-optosome-related diagnostic genes for treating CAS was vital.MethodsWe introduced transcriptome data to screen out differentially expressed genes (DEGs) in CAS. Subsequently, WGCNA analysis was utilized to mine module genes about PANoptosis score. We performed differential expression analysis (CAS samples vs. standard samples) to obtain CAS-related differentially expressed genes at the single-cell level. Venn diagram was executed to identify PAN-optosome-related differential genes (POR-DEGs) associated with CAS. Further, LASSO regression and RF algorithm were implemented to were executed to build a diagnostic model. We additionally performed immune infiltration and gene set enrichment analysis (GSEA) based on diagnostic genes. We verified the accuracy of the model genes by single-cell nuclear sequencing and RT-qPCR validation of clinical samples, as well as in vitro cellular experiments.ResultsWe identified 785 DEGs associated with CAS. Then, 4296 module genes about PANoptosis score were obtained. We obtained the 7365 and 1631 CAS-related DEGs at the single-cell level, respectively. 67 POR-DEGs were retained Venn diagram. Subsequently, 4 PAN-optosome-related diagnostic genes (CNTN4, FILIP1, PHGDH, and TFPI2) were identified via machine learning. Cellular function tests on four genes showed that these genes have essential roles in maintaining arterial cell viability and resisting cellular senescence.ConclusionWe obtained four PANoptosis-related diagnostic genes (CNTN4, FILIP1, PHGDH, and TFPI2) associated with CAS, laying a theoretical foundation for treating CAS

Distinct expression profile and histological distribution of NLRP3 inflammasome components in the tissues of Hainan black goat suggest a site-specific role in the inflammatory response

The NOD-like receptor protein 3 (NLRP3) inflammasome comprised of NLRP3, ASC and caspase-1 plays an important role in the inflammatory and innate immune response. However, little is known about the expression pattern and histological distribution of these genes in goat. Here, we first cloned the fulllength cDNAs of the NLRP3, ASC and caspase-1 genes of Hainan black goat and produced their polyclonal antibodies. Tissue-specific expression and histological distribution of these genes were analysed. Phylogenetic analysis revealed that these three goat genes had high homology with Bos taurus genes and low homology with avian or fish genes. After immunisations with these recombinant Histagged proteins, the titres of antiserum were higher than 1:1024 and purified IgG was obtained. These three genes were expressed in all examined tissues, the mRNA expression level of NLRP3 and caspase-1 was most abundant in the spleen and mesenteric lymph nodes (MLNs), while ASC was primary expressed in the liver, spleen and kidney. The histological distribution of NLRP3, ASC and caspase-1 was detected in myocardial cells, hepatocytes, focal lymphocytes, bronchiolar epithelial cells, renal tubular epithelial cells, cortical neurons and endothelial cells of the germinal centres in the MLNs. These results will be helpful in further investigations into the function of the NLRP3 inflammasome and in elucidating its role in caprine inflammatory diseases

Revisiting RGBT Tracking Benchmarks from the Perspective of Modality Validity: A New Benchmark, Problem, and Method

RGBT tracking draws increasing attention due to its robustness in multi-modality warranting (MMW) scenarios, such as nighttime and bad weather, where relying on a single sensing modality fails to ensure stable tracking results. However, the existing benchmarks predominantly consist of videos collected in common scenarios where both RGB and thermal infrared (TIR) information are of sufficient quality. This makes the data unrepresentative of severe imaging conditions, leading to tracking failures in MMW scenarios. To bridge this gap, we present a new benchmark, MV-RGBT, captured specifically in MMW scenarios. In contrast with the existing datasets, MV-RGBT comprises more object categories and scenes, providing a diverse and challenging benchmark. Furthermore, for severe imaging conditions of MMW scenarios, a new problem is posed, namely \textit{when to fuse}, to stimulate the development of fusion strategies for such data. We propose a new method based on a mixture of experts, namely MoETrack, as a baseline fusion strategy. In MoETrack, each expert generates independent tracking results along with the corresponding confidence score, which is used to control the fusion process. Extensive experimental results demonstrate the significant potential of MV-RGBT in advancing RGBT tracking and elicit the conclusion that fusion is not always beneficial, especially in MMW scenarios. Significantly, the proposed MoETrack method achieves new state-of-the-art results not only on MV-RGBT, but also on standard benchmarks, such as RGBT234, LasHeR, and the short-term split of VTUAV (VTUAV-ST). More information of MV-RGBT and the source code of MoETrack will be released at https://github.com/Zhangyong-Tang/MoETrack

Quantifying temporal variability and spatial heterogeneity in rainfall recharge thresholds in a montane karst environment

Quantifying rainfall recharge thresholds, including their spatial and temporal heterogeneity, is of fundamental importance to better understand recharge processes and improving estimation of recharge rates. Caves provide a unique observatory into the percolation of water from the surface to the water table at the timescale of individual rainfall recharge events. Here, we monitor nine infiltration sites over six years at a montane cave site in south eastern Australia. Six of the drip hydrology time series have up to ~100 hydrograph responses to rainfall over the monitoring period, three sites do not respond to rainfall events. We use two approaches to quantify rainfall recharge thresholds. At an annual timescale, for all nine drip sites, the total annual percolation water volume was determined for each year of data. Daily rainfall recharge thresholds were then determined by maximising the correlation of annual percolation water volume and total precipitation above a variable daily threshold value. The annual recharge amount methodology produced rainfall recharge thresholds for seven sites, where high and significant correlations (rank correlations > 0.75) occur for daily precipitation thresholds between 6 mm and 38 mm/day. No rainfall recharge thresholds could be obtained from one site which had a low and constant annual drip amount, and from one site which exhibited ‘underflow’ behaviour. At an event timescale, for the six sites which had a hydrograph response to rainfall, the 7-day antecedent rainfall amounts were determined. Minimum 7-day precipitation amounts prior to a hydrograph response for specific drip sites were in the range 13–28 mm and 75% of all recharge events had a 7-day antecedent precipitation between 20.7 and 38.1 mm. Combining all drip water monitoring sites and analysing the data by month identifies a seasonal variability in the minimum 7-day antecedent precipitation necessary to generate potential recharge, from 15 to 25 mm in winter to >50 mm in February and March. We apply a simple water budget model, driven by P and ET and optimised to the observed potential recharge events, to infer a ‘whole cave’ soil and epikarst storage capacity. This storage capacity is between ~50 mm (using potential evapotranspiration, 92% of events simulated successfully) to ~60 mm (using actual evapotranspiration, 79% of events simulated successfully). Modelling of individual drip sites identifies spatial heterogeneity in soil and epikarst storage capacities. Our approach using multiple methodologies allows the comparison between both daily and weekly rainfall recharge thresholds and modelled soil and epikarst storage for the first time

H9N2 avian influenza infection altered expression pattern of Sphiogosine-1-phosphate Receptor 1 in BALB/c mice

Abstract Background The pathological damage inflicted by virulent AIV strains is often caused by inducing a positive feedback loop of cytokines in immune cells that cause excessive inflammation. Previous research has shown that a G protein-coupled receptor, sphingosine-1-phosphate receptor 1 (S1PR1), plays a crucial role in the development of excessive inflammation in influenza virus infection (Cell 146:861–862, 2011; Cell 146:980–991, 2011). BALB/c mice are common laboratory animals used in research of influenza virus; however the effects of influenza infections on expression patterns of S1PR1 in mice are unknown. Methods We investigated the expression patterns of S1PR1 in normal BALB/c mice and those infected by two distinct H9N2 AIV strains, one (A/chicken/Guangdong/V/2008,V) highly pathogenic, and the other (A/chicken/Guangdong/Ts/2004,Ts), non-pathogenic in mice, using quantitative PCR and immunohistochemistry (IHC) to detect S1PR1 mRNA and protein, respectively. Results S1PR1 mRNA was ubiquitously expressed in all the tissues examined, and significant differences were seen in mRNA expression between infected Ts, V and control mice in detected tissues, heart, liver, spleen, kidney and brain. S1PR1 protein was expressed in the cytoplasm and also demonstrated quantitative changes in expression in the various tissues between mice infected with the two strains of AIV. Conclusions Our results provided the first look at differences in S1PR1 expression patterns in BALB/c mice infected by non-pathogenic and highly pathogenic H9N2 influenza viruses. This information will not only be helpful in designing experiments to better understand the role of S1PR1 in virus-host interactions but also in developing novel anti-influenza agents to minimize the mortality and morbidity associated with highly virulent strains in avian and human populations. </jats:sec

GWASdb: a database for human genetic variants identified by genome-wide association studies

Recent advances in genome-wide association studies (GWAS) have enabled us to identify thousands of genetic variants (GVs) that are associated with human diseases. As next-generation sequencing technologies become less expensive, more GVs will be discovered in the near future. Existing databases, such as NHGRI GWAS Catalog, collect GVs with only genome-wide level significance. However, many true disease susceptibility loci have relatively moderate P values and are not included in these databases. We have developed GWASdb that contains 20 times more data than the GWAS Catalog and includes less significant GVs (P < 1.0 × 10−3) manually curated from the literature. In addition, GWASdb provides comprehensive functional annotations for each GV, including genomic mapping information, regulatory effects (transcription factor binding sites, microRNA target sites and splicing sites), amino acid substitutions, evolution, gene expression and disease associations. Furthermore, GWASdb classifies these GVs according to diseases using Disease-Ontology Lite and Human Phenotype Ontology. It can conduct pathway enrichment and PPI network association analysis for these diseases. GWASdb provides an intuitive, multifunctional database for biologists and clinicians to explore GVs and their functional inferences. It is freely available at http://jjwanglab.org/gwasdb and will be updated frequently