Venenum Bufonis (VB) is a widely used traditional medicine with serious cardiotoxic effects. The inflammatory response has been studied to clarify the mechanism of the cardiotoxicity induced by VB for the first time. In the present study, Sprague Dawley (SD) rats, were administered VB (100, 200, and 400 mg/kg) intragastrically, experienced disturbed ECGs (lowered heart rate and elevated ST-segment), increased levels of serum indicators (creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and serum interleukin (IL-6, IL-1β, TNF-α) at 2 h, 4 h, 6 h, 8 h, 24 h, and 48 h, which reflected that an inflammatory response, together with cardiotoxicity, were involved in VB-treated rats. In addition, the elevated serum level of MDA and the down-regulated SOD, CAT, GSH, and GPx levels indicated the appearance of oxidative stress in the VB-treated group. Furthermore, based on the enhanced expression levels of TXNIP, p-NF-κBp65, p-IκBα, p-IKKα, p-IKKβ, p-ERK, p-JNK, and p-P38 and the obvious myocardial degeneration, it is proposed that VB-induced cardiotoxicity may promote an inflammatory response through the TXNIP/TRX/NF-κB and MAPK/NF-κB pathways. The observed inflammatory mechanism induced by VB may provide a theoretical reference for the toxic effects and clinical application of VB.

Research on orphan crops is often hindered by a lack of genomic resources. With the advent of affordable sequencing technologies, genotyping an entire genome or, for large-genome species, a representative fraction of the genome has become feasible for any crop. Nevertheless, most genotyping-by-sequencing (GBS) methods are geared towards obtaining large numbers of markers at low sequence depth, which excludes their application in heterozygous individuals. Furthermore, bioinformatics pipelines often lack the flexibility to deal with paired-end reads or to be applied in polyploid species.

Pseudogenes play a crucial role in cancer progression. However, the role of pituitary tumour-transforming 3, pseudogene (PTTG3P) in gastric cancer (GC) remains unknown. Here, we showed that PTTG3P expression was abnormally up-regulated in GC tissues compared with that in normal tissues both in our 198 cases of clinical samples and the cohort from The Cancer Genome Atlas (TCGA) database. High PTTG3P expression was correlated with increased tumour size and enhanced tumour invasiveness and served as an independent negative prognostic predictor. Moreover, up-regulation of PTTG3P in GC cells stimulated cell proliferation, migration and invasion both in vitro in cell experiments and in vivo in nude mouse models, and the pseudogene functioned independently of its parent genes. Overall, these results reveal that PTTG3P is a novel prognostic biomarker with independent oncogenic functions in GC.

Type 1 diabetes (T1D) is a metabolic disease induced by abnormal insulin secretions from damaged islet B cells. Clinical observations have shown that T1D patients are more easily infected by influenza A virus (IAV) and suffer more serious symptoms than non-T1D patients. To investigate the susceptibility of T1D mice to IAV, a T1D mouse model was built by intraperitoneal injection of diluted streptozotocin (STZ) over 5 consecutive days, followed by infection with three subtypes of IAV (H1N1/H5N1/H7N2). The T1D-infected mice showed more serious clinical symptoms and lower survival rates than the non-T1D infected mice. The hematoxylin and eosin (H&E) staining results revealed an increase in serious pathological damage to the lung and pancreas in T1D-infected mice. Immunohistochemistry results indicated higher IAV loads and a more extensive distribution of positive signals in the lungs and pancreas of T1D-infected mice than in those of non-T1D infected mice. Furthermore, according to real-time quantitative polymerase chain reaction (PCR) results, viral replication appeared to occur more easily in the lungs of T1D-infected mice. Thus, T1D-infected mice exhibited higher susceptibility to IAV than did normal mice. This study contributes a mouse model suitable for T1D research as well as valuable information about the mechanism underlying T1D patients' increased susceptibility to IAV.

As a step towards trait mapping in the halophyte seashore paspalum (Paspalum vaginatum Sw.), we developed an F1 mapping population from a cross between two genetically diverse and heterozygous accessions, 509022 and HI33. Progeny were genotyped using a genotyping-by-sequencing (GBS) approach and sequence reads were analyzed for single nucleotide polymorphisms (SNPs) using the UGbS-Flex pipeline. More markers were identified that segregated in the maternal parent (HA maps) compared to the paternal parent (AH maps), suggesting that 509022 had overall higher levels of heterozygosity than HI33. We also generated maps that consisted of markers that were heterozygous in both parents (HH maps). The AH, HA and HH maps each comprised more than 1000 markers. Markers formed 10 linkage groups, corresponding to the ten seashore paspalum chromosomes. Comparative analyses showed that each seashore paspalum chromosome was syntenic to and highly colinear with a single sorghum chromosome. Four inversions were identified, two of which were sorghum-specific while the other two were likely specific to seashore paspalum. These high-density maps are the first available genetic maps for seashore paspalum. The maps will provide a valuable tool for plant breeders and others in the Paspalum community to identify traits of interest, including salt tolerance.

Presentation of viral epitopes by swine MHC I (termed leukocyte antigen class I, SLA I) to cytotoxic T lymphocytes (CTLs) is crucial for swine immunity. The SLA-2 structure, however, remains largely unknown. To illustrate the structural basis of swine CTL epitope presentation, the crystal structure of SLA-2*04:02:02 complexed with one peptide, derived from foot-and-mouth disease virus (FMDV), was analyzed in this study. SLA-2*04:02:02 and swine β2-microglobulin (sβ2m) were refolded in vitro in the presence of peptides. X-ray diffraction data of SLA-2*04:02:02-peptide-sβ2m (referred to as p/SLA-2*04:02:02) were collected. The diffraction dataset was 2.3 Å in resolution and the space group was P3(2)21. Relevant data included a = 101.8 Å, b = 101.8 Å, c = 73.455 Å,α = 90.00°, β = 90.00°, γ = 120.00°. The structure of p/SLA-2*04:02:02 was analyzed. The results revealed that Glu24, Met68, Gly76, and Gln173 in PBG of SLA-2*04:02:02 are different from other MHC I. Furthermore, Asn63 is different from other SLA I. Gln57, Met174 and Gln180 in PBG of SLA I are different from other species' MHC I. All of these features are different from known mammalian peptide-MHC class I complexes (referred to as p/MHC I). In addition, P4-His, P6-Val, and P8-Pro in the peptide were exposed, and these residues as epitopes can be presented by SLA-2*04:02:02. This study not only provides a structural basis for peptide presentation by SLA-2, but also screens one potential FMDV CTL epitope. The results may be of interest in future vaccine development.

Diabetic retinopathy (DR) is a serious blinding complication of diabetes. At present, the therapeutic intervention effect is limited. We aimed to investigate the circRNA expression profiles in retinal proliferative fibrovascular membranes of patients with DR and explore the effect of circFAT1 on pyroptosis and autophagy of high glucose (HG)-induced retinal pigment epithelial (RPE) cells and its molecualr mechanism. In this study, circRNA sequencing was performed to determine the expression profiles of circRNAs in DR patients. The expression of circFAT1 was measured by qRT-PCR. Cell counting kit-8, transmission electron microscope, western blot, immunofluorescence and enzyme-linked immunosorbent assay were conducted to explore the roles of HG and circFAT1 in RPE cell pyroptosis and autophagy. RNA pull down was used to determine the binding protein of circFAT1. Our data showed that HG significantly reduced the viability of RPE cells, inhibited cell autophagy and contributed to cell pyroptosis. In addition, a total of 189 differentially expressed circRNAs (DEcircRNAs) were identified between DR patients and non-DR patients, including 93 upregulated and 96 downregulated DEcircRNAs in the retinal proliferative fibrovascular membranes of DR patients. Pathway analysis showed that DEcircRNAs were mainly involved in MAPK signaling pathway, TGF-beta signaling pathway and adherens junction. Moreover, circFAT1 was significantly downregulated in retinal proliferative fibrovascular membranes of DR patients and HG-induced RPE cells. CircFAT1 overexpression remarkably enhanced the expression of LC3B, while reduced the expression of GSDMD in HG-induced RPE cells. RNA pull down combined with western blot analysis indicated that circFAT1 bound to m6A reader YTHDF2. YTHDF2 overexpression significantly increased the protein expression of LC3B in HG-induced RPE cells. In summary, circFAT1 promoted autophagy and inhibited pyroptosis of RPE cells induced by HG, and could combine with YTHDF2. This study provides new ideas for DR prevention and treatment.

Heart failure is caused by acute or chronic cardiovascular diseases with limited treatments and unclear pathogenesis. Therefore, it is urgent to explore new therapeutic targets and reveal new pathogenesis for heart failure.

In plants, age-related resistance (ARR) refers to a gain of disease resistance during shoot or organ maturation. ARR associated with vegetative phase change, a transition from juvenile to adult stage, is a widespread agronomic trait affecting resistance against multiple pathogens. How innate immunity in a plant is differentially regulated during successive stages of shoot maturation is unclear. In this work, we found that Arabidopsis thaliana showed ARR against its bacterial pathogen Pseudomonas syringae pv. tomato DC3000 during vegetative phase change. The timing of the ARR activation was associated with a temporal drop of miR156 level. The microRNA miR156 maintains juvenile phase by inhibiting the accumulation and translation of SPL transcripts. A systematic inspection of the loss- and gain-of-function mutants of 11 SPL genes revealed that a subset of SPL genes, notably SPL2, SPL10, and SPL11, activated ARR in adult stage. The immune function of SPL10 was independent of its role in morphogenesis. Furthermore, the SPL10 mediated an age-dependent augmentation of the salicylic acid (SA) pathway partially by direct activation of PAD4. Disrupting SA biosynthesis or signaling abolished the ARR against Pto DC3000. Our work demonstrated that the miR156-SPL10 module in Arabidopsis is deployed to operate immune outputs over developmental timing.

Atrial fibrillation (AF) is the most common type of heart arrhythmia. Currently, the pathogenesis of AF is not fully understood yet. A growing body of evidence highlighted the strong association between inflammation and the pathogenesis of AF. C-reactive protein (CRP) is an inflammation marker with increased expression in AF. Therefore, the aim of this study was to determine if CRP promotes inflammation, which may sequentially mediate the onset of AF and the concurrent atrial fibrosis, through TLR4/NF-κB/TGF-β pathway. HL-1 cells were treated with either 25 or 50 μg/ml recombinant human CRP. TGF-β1 and NF-κB inhibitors were given either solely or together to the 50 μg/ml CRP-treated cells. Cell proliferation, apoptosis, the expression of apoptotic factors and TLR4, IL-6, TGF-β1, Smad2, and the phosphorylation of Smad2 were determined. Data showed that CRP induced dose-dependent inhibition on cell proliferation and promoted cell apoptosis, which was induced through both intrinsic and extrinsic pathways. Such effects were reversed by inhibiting TGF-β1 and/or NF-κB. Inhibition of TGF-β1 and/or NF-κB also reduced the expression of TLR4 and IL-6. Inhibition of NF-κB alone weakened the expression of TGF-β1 and phosphorylation of Smad2. Our study demonstrated that CRP is not only a marker, but also an important mediator in the induction of inflammation and likely the pathogenesis of AF. We for the first time reported CRP-induced activation and cross-talk between TLR4 and NF-κB/TGF-β1 signaling pathway in a cardiomyocyte model. Reducing CRP and targeting TLR4/NF-κB/TGF-β1 pathway may provide new insights in the therapeutic interventions to inflammation-induced AF.

New approaches are urgently needed to fight influenza viral infection. Previous research has shown that zirconia nanoparticles can be used as anticancer materials, but their antiviral activity has not been reported. Here, we investigated the antiviral effect of zirconia (ZrO2) nanoparticles (NPs) against a highly pathogenic avian influenza virus.

Eremurus species, better known as 'Foxtail Lily' or 'Desert Candle', are important worldwide in landscaping and the cut-flower industry. One of the centers of highest diversity of the genus Eremurus is Iran, which has seven species. However, little is known about the genetic diversity within the genus Eremurus. With the advent of genotyping-by-sequencing (GBS), it is possible to develop and employ single nucleotide polymorphism (SNP) markers in a cost-efficient manner in any species, regardless of its ploidy level, genome size or availability of a reference genome. Population structure and phylogeographic analyses of the genus Eremurus in Iran using a minimum of 3002 SNP markers identified either at the genus level or at the species level from GBS data showed longitudinal geographic structuring at the country scale for the genus and for the species E. spectabilis and E. luteus, and at the regional scale for E. olgae. Our analyses furthermore showed a close genetic relatedness between E. olgae and E. stenophyllus to the extent that they should be considered subspecies within an E. olgae/stenophyllus species complex. Their close genetic relatedness may explain why crosses between these two (sub)species have been found in the wild and are exploited extensively as ornamentals. Last, current species identification, while robust, relies on flower morphology. A subset of seven SNPs with species-specific (private) alleles were selected that differentiate the seven Eremurus species. The markers will be especially useful for cultivar protection and in hybrid production, where true hybrids could be identified at the seedling stage.

Aegilops tauschii is the diploid progenitor of the D genome of hexaploid wheat (Triticum aestivum, genomes AABBDD) and an important genetic resource for wheat. The large size and highly repetitive nature of the Ae. tauschii genome has until now precluded the development of a reference-quality genome sequence. Here we use an array of advanced technologies, including ordered-clone genome sequencing, whole-genome shotgun sequencing, and BioNano optical genome mapping, to generate a reference-quality genome sequence for Ae. tauschii ssp. strangulata accession AL8/78, which is closely related to the wheat D genome. We show that compared to other sequenced plant genomes, including a much larger conifer genome, the Ae. tauschii genome contains unprecedented amounts of very similar repeated sequences. Our genome comparisons reveal that the Ae. tauschii genome has a greater number of dispersed duplicated genes than other sequenced genomes and its chromosomes have been structurally evolving an order of magnitude faster than those of other grass genomes. The decay of colinearity with other grass genomes correlates with recombination rates along chromosomes. We propose that the vast amounts of very similar repeated sequences cause frequent errors in recombination and lead to gene duplications and structural chromosome changes that drive fast genome evolution.

This study aimed to identify independent predictors for the risk of hemorrhagic transformation (HT) in arterial ischemic stroke (AIS) patients.

Pearl millet [Cenchrus americanus (L.) Morrone] is a staple food for more than 90 million farmers in arid and semi-arid regions of sub-Saharan Africa, India and South Asia. We report the ∼1.79 Gb draft whole genome sequence of reference genotype Tift 23D2B1-P1-P5, which contains an estimated 38,579 genes. We highlight the substantial enrichment for wax biosynthesis genes, which may contribute to heat and drought tolerance in this crop. We resequenced and analyzed 994 pearl millet lines, enabling insights into population structure, genetic diversity and domestication. We use these resequencing data to establish marker trait associations for genomic selection, to define heterotic pools, and to predict hybrid performance. We believe that these resources should empower researchers and breeders to improve this important staple crop.

Objectives: To develop an efficient and quantitative assessment of collateral circulation on time maximum intensity projection CT angiography (tMIP CTA) in patients with acute ischemic stroke (AIS). Methods: Eighty-one AIS patients who underwent one-stop CTA-CT perfusion (CTP) from February 2016 to October 2020 were retrospectively reviewed. Single-phase CTA (sCTA) and tMIP CTA were developed from CTP data. Ischemic core (IC) volume, ischemic penumbra volume, and mismatch ratio were calculated. The Tan scale was used for the qualitative evaluation of collateral based on sCTA and tMIP CTA. Quantitative collateral circulation (CCq) parameters were calculated semi-automatically with software by the ratio of the vascular volume (V) on both hemispheres, including tMIP CTA VCCq and sCTA VCCq. Spearman correlation analysis was used to analyze the correlation of collateral-related parameters with final infarct volume (FIV). ROC and multivariable regression analysis were calculated to compare the significance of the above parameters in clinical outcome evaluation. The analysis time of the observers was also compared. Results: tMIP CTA VCCq (r = 0.61, p < 0.01), IC volume (r = 0.66, p < 0.01), Tan score on tMIP CTA (r = 0.52, p < 0.01) and mismatch ratio (r = 0.60, p < 0.01) showed moderate negative correlations with FIV. tMIP CTA VCCq showed the best prognostic value for clinical outcome (AUC = 0.93, p < 0.001), and was an independent predictive factor of clinical outcome (OR = 0.14, p = 0.009). There was no difference in analysis time of tMIP CTA VCCq among observers (p = 0.079). Conclusion: The quantitative evaluation of collateral circulation on tMIP CTA is associated with clinical outcomes in AIS patients with endovascular treatments.

The prevalence of intracranial aneurysms is approximately 3% worldwide. Posterior circulation (PC) aneurysms have a higher risk of treatment complications than anterior circulation aneurysms. Improving the survival rate and quality of life of patients with PC aneurysms remains one of the most important issues in the field.

Cholangiocarcinoma (CCA) is one of the most common histological types of primary hepatic malignancy and is associated with poor overall prognosis, causing a ponderous burden on human life. Hence, it is necessary to elucidate the pathogenesis of CCA. The objective of our research was to shed light on the mechanism through which long non-coding RNA titin-antisense RNA1 (lncRNA TTN-AS1) is involved in the development of CCA. Reverse transcription quantitative polymerase chain reaction was used to detect TTN-AS1 expression in CCA samples and cells. Functional experiments were performed using the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, transwell, and in vivo tumor growth assays. The relationship between TTN-AS1, miR-513a-5p, and stratifin (SFN) was explored using a dual luciferase reporter assay, RNA immunoprecipitation (RIP) experiment, and Pearson correlation analysis. The result showed that TTN-AS1 and SFN are highly expressed in CCA tissues. Bioinformatics analysis, luciferase reporter and RIP experiments revealed the correlation between TTN-AS1, miR-513a-5p, and SFN. In addition, silencing TTN-AS1 mitigated CCA cell proliferation and migration. Mechanistically, miR-513a-5p is sponged by TTN-AS1. The miR-513a-5p inhibitor abolished the effect of TTN-AS1 silencing on the aggressive behaviors of CCA cells. Furthermore, we showed that miR-513a-5p is a regulator of CCA by targeting SFN. TTN-AS1 induced CCA cell growth and metastasis via the miR-513a-5p/SFN pathway, which offers a new strategy for therapeutic interventions for CCA.

The inflammatory response and apoptosis have been proved to have a crucial role in the pathogenesis of the influenza A virus (IAV). Previous studies indicated that while IAV commonly causes pancreatitis and pancreatic damage in naturally and experimentally infected animals, the molecular mechanisms of the pathogenesis of IAV infection are less reported. In the present study, we showed for the first time that both avian-like (α-2,3-linked) and human-like (α-2,6-linked) sialic acid (SA) receptors were expressed by the mouse pancreatic cancer cell line PAN02 and the human pancreatic cancer cell line PANC-1. Using growth kinetics experiments, we also showed that PAN02 and PANC-1 cells supported the productive replication of the H5N1 highly pathogenic avian influenza while exhibited the limited replication of IAV subtypes H1N1 and H7N2 in vitro. The in vivo infection of H5N1 in pancreatic cells was confirmed by the histopathological and immunohistochemical staining of pancreas tissue from mice. Other than H1N1 and H7N2, severe damage and extensive positive signals were observed in pancreas of H5N1 infected mice. All three virus subtypes induced apoptosis but also triggered the infected PAN02 and PANC-1 cells to release pro-inflammatory cytokines and chemokines including interferon (IFN)-α, IFN-β, IFN-γ, chemokine (C-C motif) ligand 2 (CCL2), tumor necrosis factor (TNF)-α, and interleukin (IL)-6. Notably, the subtypes of H5N1 could significantly upregulate these cytokines and chemokines in both two cells when compared with H1N1 and H7N2. The present data provide further understanding of the pathogenesis of H5N1 IAV in pancreatic cells derived from humans and mammals and may also benefit the development of new treatment against H5N1 influenza virus infection.

Long non-coding RNAs (lncRNAs) are recently discovered RNA transcripts that are aberrantly expressed in many tumor types. Numerous studies have suggested that lncRNAs can be utilized for cancer diagnosis and prognosis. LSINCT5 (long stress-induced non-coding transcript 5) is dramatically upregulated in breast and ovarian cancer and affects cellular proliferation. However, the expression pattern of LSINCT5 in gastrointestinal cancer and the association between aberrant expression of LSINCT5 in gastrointestinal cancer and malignancy, metastasis, or prognosis remain unknown. LSINCT5 expression was detected in gastrointestinal cancer and paired adjacent normal tissue samples or cell lines using reverse transcription quantitative PCR (RT-qPCR). We also investigated the potential relationship between tumor LSINCT5 levels and clinicopathological features of gastrointestinal cancer. Finally, we assessed whether LSINCT5 influences in vitro cell proliferation. The expression of LSINCT5 is significantly upregulated in gastrointestinal cancer tissues and cell lines relative to their normal counterparts. In addition, increased LSINCT5 expression was correlated with a larger tumor size, deeper tumor depth, and advanced clinical stage. Kaplan-Meier analysis indicated that gastric cancer (GC) and colorectal cancer (CRC) patients with higher LSINCT5 expression levels have worse disease-free survival (DFS) and disease-specific survival (DSS) rates. Moreover, multivariate analysis revealed that increased expression of LSINCT5 is an independent predictor of DFS and DSS rates in GC patients. The ectopic expression of LSINCT5 in gastrointestinal cancer cell lines resulted in an increase in cellular proliferation; conversely, knock down of LSINCT5 significantly inhibited proliferation. These results suggest that LSINCT5 may represent a novel prognostic indicator and a target for gene therapy in gastrointestinal cancer.