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Many disease resistance genes have been introgressed into wheat from its wild relatives. However, reduced recombination within the introgressed segments hinders the cloning of the introgressed genes. Here, we have cloned the powdery mildew resistance gene Pm13, which is introgressed into wheat from Aegilops longissima, using a method that combines physical mapping with radiation-induced chromosomal aberrations and transcriptome sequencing analysis of ethyl methanesulfonate (EMS)-induced loss-of-function mutants. Pm13 encodes a kinase fusion protein, designated MLKL-K, with an N-terminal domain of mixed lineage kinase domain-like protein (MLKL_NTD domain) and a C-terminal serine/threonine kinase domain bridged by a brace. The resistance function of Pm13 is validated through transient and stable transgenic complementation assays. Transient over-expression analyses in Nicotiana benthamiana leaves and wheat protoplasts reveal that the fragment Brace-Kinase122-476 of MLKL-K is capable of inducing cell death, which is dependent on a functional kinase domain and the three α-helices in the brace region close to the N-terminus of the kinase domain. The powdery mildew resistance gene Pm13 was introgressed into wheat from Aegilops longissima. Here, the authors report the cloning of Pm13 and reveal that it encodes a MLKL_NTD domain-containing kinase. [ABSTRACT FROM AUTHOR]

Primary gastric adenosquamous carcinoma (PGASC) is a rare type of gastric cancer with limited research and poorly understood clinicopathological features. This study investigated the clinicopathological features and outcomes of PGASC. Patients with PGASC from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and from the published literature were enrolled in this study. Survival curves were generated using the Kaplan–Meier method, and prognostic factors were identified through Cox proportional hazards regression models. This study identified 76 eligible cases of PGASC, with 45 cases from published literature and 31 from our center. The most prevalent symptoms were abdominal pain and dysphagia, with a median age of 62 years (range: 29–84 years). The primary lesions were predominantly in the proximal stomach, with a median tumor size of 6.5 cm (range: 1.5–16.0 cm). Tumor stages II, III, and IV were detected in 12 (16.7%), 43 (59.7%), and 17 (23.6%) patients, respectively. Most tumors were poorly differentiated in both the squamous cell carcinoma (SCC) component and adenocarcinoma (AC) component. The median survival time was 17 months (range: 2–122 months). The 1, 3, and 5-year overall survival (OS) was 60.7%, 31.1%, and 24.1%, respectively. Multivariate analysis revealed that OS was independently predicted by the proportion of SCC component, differentiation of AC component, and tumor stage. PGASC is a rare disease with a poor prognosis. A high proportion of SCC components, low differentiated AC components, and advanced tumor were associated with worse survival in patients with PGASC. Adjuvant therapy did not improve survival time. [ABSTRACT FROM AUTHOR]

The Spoofing-Aware Speaker Verification (SASV) system is designed to protect automatic speaker verification (ASV) systems from potential speech spoofing attacks by integrating the ASV and countermeasure systems. The optimization of the ASV system can further enhance the resistance of the SASV system to various spoofing methods. Thus, an Attentional Multi-Feature Fusion framework is proposed in this paper to enhance the speech feature content in the ASV system, aiming to mitigate security vulnerabilities. Furthermore, for feature modeling, we introduce the Conformer module, which combines convolutional neural networks and Transformers to effectively capture both local and global features while extracting fixed-dimensional speaker embedding vectors. The experimental results demonstrate that the proposed ASV system achieves a nearly 25% improvement compared to the baseline ASV system. Furthermore, the SASV system, based on the proposed ASV system, demonstrates nearly 33% and 34% improvements in spoofing awareness with score-based fusion and embedding-based fusion strategies, respectively. This implies that the improved SASV system is capable of detecting and recognizing speech-spoofing attacks more effectively. [ABSTRACT FROM AUTHOR]

Unidirectional surface waves in nonreciprocal plasmonic platforms with nonlocal effects have been a topic of significant interest and some controversy. In this study, we present a scheme to achieve unidirectional surface magnetoplasmons (USMPs) with large modal areas at terahertz frequencies. Such large-area USMPs (LUSMPs) exist in a metal-UENZ (uniaxial- ε -near-zero)-Si-InSb structure under external magnetic field, where the effect of nonlocality is included. The field of the LUSMP extends almost uniformly in the UENZ layer with a thickness of wavelength scale, thus its modal size can be represented by the UENZ-layer thickness. Due to the modal energy primarily distributed in the thick UENZ layer, the nonlocality-induced leakage of the LUSMP is significantly reduced by an order of magnitude, compared to previous USMP existing at interface between InSb and opaque isotropic medium. Due to their large modal sizes, such LUSMPs can be efficiently excited by terahertz radiations directly from free space. In addition, LUSMPs offer high degree of freedom for manipulating terahertz waves, such as energy squeezing and trapping. Based on LUSMPs, a terahertz free-space isolator is also developed. Our findings have important implications to the development of innovative plasmonic devices in terahertz regime. [ABSTRACT FROM AUTHOR]

The existing biomarkers are insufficient for predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary mucinous neoplasm (IPMN) is a precursor to PDAC; therefore, identifying biomarkers from differentially expressed genes (DEGs) of PDAC and IPMN is a new and reliable strategy for predicting the prognosis of PDAC. In this study, four datasets were downloaded from the Gene Expression Omnibus database and standardized using the R package 'limma.' A total of 51 IPMN and 81 PDAC samples were analyzed, and 341 DEGs in PDAC and IPMN were identified; DEGs were involved in the extracellular matrix and tumor microenvironment. An acceptable survival prognosis was demonstrated by SDC1 and ITGA2, which were highly expressed during in vitro PDAC cell proliferation, apoptosis, and migration. SDC1high was enriched in interferon alpha (IFN-α) response and ITGA2high was primarily detected in epithelial-mesenchymal transition (EMT), which was verified using western blotting. We concluded that SDC1 and ITGA2 are potential prognostic biomarkers for PDAC associated with IPMN. Downregulation of SDC1 and ITGA2 expression in PDAC occurs via a mechanism involving possible regulation of IFN-α response, EMT, and immunity, which may act as new targets for PDAC therapy. [ABSTRACT FROM AUTHOR]

Ginger (Zingiber officinale) is one of the most widely consumed dietary supplements. However, the content of active ingredients varied greatly from place to place. In this study, we first identified and compared the compositions of ginger samples from six different origins. Then, we evaluated the anti-inflammatory activity of different samples in LPS-stimulated RAW264.7 cells. The results indicated that highly variable in chemical composition and activity for ginger from different origin. Further, correlation analysis showed that isoborneol, terpineol, α-curcumene, germacrene D, α-elemol and 8-shogaol exhibited a strong correlation with inflammatory factors, which could be used as potential chemical markers to evaluate quality and distinguish source of ginger. Finally, comprehensive evaluation found that the ginger from Sichuan exerts stronger anti-inflammatory properties. This study will help to select ginger varieties with excellent characteristics, provide theoretical basis for the development and utilization of ginger. [ABSTRACT FROM AUTHOR]

Circulating microRNAs (miRNAs) have been considered potential markers for the early detection of malignant colorectal cancer (CRC). We aimed to identify a group of miRNAs for the early detection of CRC and assess their predictive ability in a community-based population in China. A nested case‒control study consisting of 97 incident colorectal cancer cases and 103 frequency-matched healthy controls was conducted. The data were randomly assigned into a training set (60%) and a test set (40%). We selected and detected 10 kinds of miRNAs in plasma samples. Multivariate logistic regression analysis was used to identify miRNAs associated with colorectal cancer risk in the training set and test set. Then, we evaluated the predictive ability of the identified miRNAs by the receiver operating characteristic curve (ROC). In this study, three miRNAs (miRNA-29a, miRNA-125b, miRNA-145) were significantly associated with colorectal cancer risk in both the training set and test set. The sensitivity of the identified miRNAs ranged from 0.854 to 0.961. After adding the identified miRNAs, the AUC (area under the curve) value significantly increased from 0.61 to 0.71 compared with the basic model consisting of only basic demographic information. We identified a three-plasma miRNA signature that may serve as a novel non-invasive biomarker in early CRC detection and in predicting individual CRC risk in the generation population. [ABSTRACT FROM AUTHOR]

Background: Bronchial washing fluid (BWF) is a less-invasive specimen. Due to the limited sensitivity of BWF cellular component diagnosis, the aim of this study was to explore the potential role of BWF supernatant as a source of liquid biopsy of lung cancer. Methods: This prospective study enrolled 76 suspected and 5 progressed lung cancer patients. Transbronchial biopsy tissues, BWF supernatant (BWF_Sup) and BWF precipitant (BWF_Pre) were tested by a targeted panel of 1021 genes. Results: BWF_Sup cell-free DNA (cfDNA) was superior to tissue biopsy and BWF_Pre in determining mutational allele frequency, tumour mutational burden, and chromosomal instability. Moreover, BWF_Sup and BWF_Pre achieved comparable efficacy to tissue samples in differentiating malignant and benign patients, but only BWF_Sup persisted differentiated performance after excluding 55 malignancies pathologically diagnosed by bronchoscopic biopsy. Among 67 malignant patients, 82.1% and 71.6% of tumour-derived mutations (TDMs) were detected in BWF_Sup and BWF_Pre, respectively, and the detectability of TDMs in BWF_Sup was independent of the cytological examination of BWF. BWF_Sup outperformed BWF_Pre in providing more subclonal information and thus might yield advantage in tracking drug-resistant markers. Conclusions: BWF_Sup cfDNA is a reliable medium for lung cancer diagnosis and genomic profiles and may provide important information for subsequent therapeutic regimens. [ABSTRACT FROM AUTHOR]

To establish a prognostic model based on immune-related microRNA (miRNA) for pancreatic carcinoma. Weighted correlation network analysis (WGCNA) was performed using the "WGCNA" package to find the key module genes involved in pancreatic carcinoma. Spearman correlation analysis was conducted to screen immune-related miRNAs. Uni- and multi-variate COX regression analyses were carried out to identify miRNAs prognostic for overall survival (OS) of pancreatic carcinoma, which were then combined to generate a prognostic model. Kaplan–Meier survival analysis, receiver operating characteristic (ROC) analysis, distribution plot of survival status in patients and regression analysis were collectively performed to study the accuracy of the model in prognosis. Target genes of the miRNAs in the model were intersected with the key module genes, and a miRNA–mRNA network was generated and visualized by Cytoscape3.8.0. TIMER analysis was conducted to study the abundance of immune infiltrates in tumor microenvironment of pancreatic carcinoma. Expression levels of immune checkpoint genes in subgroups stratified by the model were compared by Wilcoxon test. Gene Set Enrichment Analysis (GSEA) was performed to analyze the enriched signaling pathways between subgroups. Differential analysis revealed 1826 genes differentially up-regulated in pancreatic carcinoma and 1276 genes differentially down-regulated. A total of 700 immune-related miRNAs were obtained, of which 7 miRNAs were significantly associated with OS of patients and used to establish a prognostic model with accurate predictive performance. There were 99 mRNAs overlapped from the 318 target genes of the 7 miRNAs and the key modules genes analyzed by WGCNA. Patient samples were categorized as high or low risk according to the prognostic model, which were significantly associated with dendritic cell infiltration and expression of immune checkpoint genes (TNFSF9, TNFRSF9, KIR3DL1, HAVCR2, CD276 and CD80). GSEA showed remarkably enriched signaling pathways in the two subgroups. This study identified an immune-related 7-miRNA based prognostic model for pancreatic carcinoma, which could be used as a reliable tool for prognosis. [ABSTRACT FROM AUTHOR]

Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease1–7, evidence of lupus-causing TLR7 gene variants is lacking. Here we describe human systemic lupus erythematosus caused by a TLR7 gain-of-function variant. TLR7 is a sensor of viral RNA8,9 and binds to guanosine10–12. We identified a de novo, previously undescribed missense TLR7Y264H variant in a child with severe lupus and additional variants in other patients with lupus. The TLR7Y264H variant selectively increased sensing of guanosine and 2',3'-cGMP10–12, and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c+ age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7Y264H mice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.The missense TLR7Y264H gain-of-function genetic variation causes systemic lupus erythematosus in humans and mice. [ABSTRACT FROM AUTHOR]

Water colour is the result of its constituents and their interactions with solar irradiance; this forms the basis for water quality monitoring using optical remote sensing data. The Forel-Ule Index (FUI) is a useful comprehensive indicator to show the water colour variability and water quality change in both inland waters and oceans. In recent decades, lakes around the world have experienced dramatic changes in water quality under pressure from both climate change and anthropogenic activities. However, acquiring consistent water colour products for global lakes has been a challenge. In this paper we present the first time series FUI dataset for large global lakes from 2000–2018 based on MODIS observations. This dataset provides significant information on spatial and temporal changes of water colour for global large lakes during the past 19 years. It will be valuable to studies in search of the drivers of global and regional lake colour change, and the interaction mechanisms between water colour, hydrological factors, climate change, and anthropogenic activities. Measurement(s) color Technology Type(s) satellite imaging Factor Type(s) temporal interval Sample Characteristic - Environment water body • lake Sample Characteristic - Location global Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13257218 [ABSTRACT FROM AUTHOR]

Bacillus velezensis LPL061, which shows strong exopolysaccharide (EPS) producing capacity, was isolated from carnations in Beijing, China. The complete genome of LPL061 comprised a single circular chromosome (3,907,268 bp; G+C content of 46.7%) with 3,737 coding DNA sequences, 26 rRNA, and 89 tRNA. According to genome analysis, 12 protein-coding genes which related to polysaccharide biosynthesis in LPL061 were identified. Comparative genome analysis revealed that the EPS biosynthetic gene cluster was relatively conserved among Bacillus species. EPS showed approximately 60% inhibitory activity on the α-glucosidase at 100 μg/mL. The results of quantitative reverse transcription PCR further demonstrated that compared to insulin-resistant model with insulin (500 μg/mL) (without EPS treatment), the insulin-resistant HepG2 cells treated with EPS decreased the expression of phosphoenolpyruvate carboxykinase (PEPCK) from 4.425 to 0.1587, glucose-6-phosphatase (G6Pase) decreased from 4.272 to 0.1929, and glycogen synthase kinase3β (GSK(3)β) decreased from 2.451 to 0.993, respectively. Meanwhile, EPS treatment increased GS expression and resulted in intracellular glycogen concentration increased from 28.30% to 86.48%, which further supported that EPS form LPL061 could reduce the concentration of blood glucose effectively. These results could be beneficial for better understanding of the hypoglycemic mechanism of B. velezensis LPL061 EPS and developing an EPS-based anti-diabetic agent in the future. [ABSTRACT FROM AUTHOR]

SmCo7/Co nanocomposite powders were prepared by high-energy ball milling of SmCo5 modified by adding Co and annealed at different temperatures. The phase evolution, microstructure and magnetic properties of the nanocomposite powders were analyzed. The results have shown that the annealing temperature and the addition of Co significantly affected the phase structures and magnetic properties of the powders. The nanocomposite powders were completely composed of the SmCo7 phase and the face-centered cubic Co phase. When annealing the SmCo5 powder at 750 °C, the SmCo7 phase decomposed into Th2Zn17-type Sm2Co17 and CaCu5-type SmCo5 phases with an average grain size of 13.9 nm, and the maximum energy product and remanence had maximum values of 10.51 MGOe and 77.92 emu/g, respectively. However, adding 28 wt% Co effectively prevented growth of the grain (11.5 nm) and enhanced the decomposition temperature (850 °C), resulting in a higher maximum magnetic energy product, coercivity, and remanence. The SmCo7 lattice contracted as Co content increased. [ABSTRACT FROM AUTHOR]

Weakening and leveling of the halogen bond (XB) between diiodoperfluoroalkane (DIPFA) and halide anions (X, X = Cl, Br and I) are imposed by solvent polarity. The solvents involved in this system are classified into three groups according to the acceptor number ( AN) and solvent HB acidity (α) and were studied in detail. In non-competitive solvents, the strength of C-I···X XB is strongest, decreasing with electrostatic interaction in the order: C-I···Cl > C-I···Br > C-I···I. However, in weakly competitive solvents, the XB strength is largely weakened. Further, in strongly competitive solvents, the XB strength is leveled with no change occurring with X. This phenomenon can be attributed to the solvent effect. That is, the solvent can destabilize the DIPFA···X XB. This was confirmed by the experiment showing that the XB was destroyed as very small amounts of water was added into the CHCN solution of DIPFA and X. [ABSTRACT FROM AUTHOR]

Purpose: High mobility group box-1 (HMGB1) is a proinflammatory, DAMP protein that participates in many pathological conditions. In this study, we evaluated the usability of CSF HMGB1 as a biomarker for the diagnosis of tuberculous meningitis (TBM). Methods: A total of 59 TBM patients and 169 control patients were included in our study. CSF samples were obtained and analyzed for HMGB1 using a commercial ELISA kit. Results: The mean CSF HMGB1 was 19.36 ng/ml in TBM patients (n = 59) versus 3.12 ng/ml in non-TB meningitis patients (n = 30), 2.13 ng/ml in patients with extra neural tuberculosis (n = 73), and 1.06 ng/m in controls (n = 66). According to the receiver operator characteristic curves, a cut-off value of 3.4 ng/ml was calculated, indicating that the sensitivity and specificity of CSF HMGB1 alone in diagnosis of TBM were 61.02 and 89.94 %, respectively. In patients with extra neural tuberculosis and a high risk of TBM, CSF HMGB1 seemed to be a good candidate for early differential diagnosis of TBM at the cut-off value of 3.8 ng/ml, when the sensitivity and specificity were 79.49 and 94.52 % respectively. Conclusion: Our finding may prove to be clinically useful, because CSF HMGB1 ELISA can be performed in almost all clinical laboratories, especially when sophisticated technologies are either time consuming or unavailable. [ABSTRACT FROM AUTHOR]

Aim:To investigate the molecular mechanisms underlying the influence of DNA polymerase from different genotypes of hepatitis B virus (HBV) on the binding affinity of adefovir (ADV).Methods:Computational approaches, including homology modeling, docking, MD simulation and MM/PBSA free energy analyses were used.Results:Sequence analyses revealed that residue 238 near the binding pocket was not only a polymorphic site but also a genotype-specific site (His238 in genotype B; Asn238 in genotype C). The calculated binding free-energy supported the hypothesis that the polymerase from HBV genotype C was more sensitive to ADV than that from genotype B. By using MD simulation trajectory analysis, binding free energy decomposition and alanine scanning, some energy variation in the residues around the binding pocket was observed. Both the alanine mutations at residues 236 and 238 led to an increase of the energy difference between genotypes C and B (ΔΔGC-B), suggesting that these residues contributed to the genotype-associated antiviral variability with regard to the interaction with ADV.Conclusion:The results support the hypothesis that the HBV genotype C polymerase is more sensitive to ADV than that from genotype B. Moreover, residue N236 and the polymorphic site 238 play important roles in contributing to the higher sensitivity of genotype C over B in the interaction with ADV. [ABSTRACT FROM AUTHOR]

MP2(full)/aug-cc-pVDZ(-PP) computations predict that new triangular bonding complexes [InlineMediaObject not available: see fulltext.] (where X is a halide and H-C refers to a protic solvent molecule) consist of one halogen bond and two hydrogen bonds in the gas phase. Carbon tetrabromide acts as the donor in the halogen bond, while it acts as an acceptor in the hydrogen bond. The halide (which commonly acts as an acceptor) can interact with both carbon tetrabromide and solvent molecule (CHCN, CHCl, CHCl) to form a halogen bond and a hydrogen bond, respectively. The strength of the halogen bond obeys the order CBr⋅⋅⋅Cl > CBr⋅⋅⋅Br > CBr⋅⋅⋅I. For the hydrogen bonds formed between various halides and the same solvent molecule, the strength of the hydrogen bond obeys the order C-H⋅⋅⋅Cl > C-H⋅⋅⋅Br > C-H⋅⋅⋅I. For the hydrogen bonds formed between the same halide and various solvent molecules, the interaction strength is proportional to the acidity of the hydrogen in the solvent molecule. The diminutive effect is present between the hydrogen bonds and the halogen bond in chlorine and bromine triangular bonding complexes. Complexes containing iodide ion show weak cooperative effects. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The major exopolysaccharide fraction (EPSa) of Bifidobacterium animalis RH was purified to illustrate the chemical characterization and the antioxidant activity in vitro. The molecular weight of EPSa was 2.31 × 10 Da determined by the gel permeation chromatography (GPC). Fourier-transform infrared spectra (FT-IR) and the monosaccharide analysis of high-pH anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) showed that it was a heteropolysaccharide mainly composed of d-glucose, d-mannose, d-galactose, l-arabinose, d-fructose, and l-rhamnose in molar ratios of 43:34:18:4:1:1. In antioxidant assays, the EPSa had a higher activity for antilipid peroxidation and a stronger scavenging activity of hydroxyl radical and superoxide radical than ascorbic acid. It also had a similar α,α-diphenyl-β-picrylhydrazyl (DPPH) radical-scavenging activity with ascorbic acid at low concentration and had concentration-dependent inhibitory ability on erythrocyte hemolysis. These results indicated that the EPSa fraction had strong antioxidant activities and could be explored as novel potential antioxidants. [ABSTRACT FROM AUTHOR]

A microwave one-way waveguide of three-dimensional configuration is proposed and investigated theoretically. In this waveguide there exists a complete one-way propagation band, where the mode propagates only in one direction and can be immune to backscattering. By terminating the one-way waveguide with metal slab, one-way propagating waves in this waveguide system can be stopped at the terminal end without any backscattering. Meanwhile, a hotspot with extremely enhanced magnetic-field amplitude is generated in this 3D waveguide system. For an incident microwave pulse, the trapped wave packet can be compressed to deep subwavelength scale besides the magnetic field enhancement. Moreover, the magnetic field enhancement of trapped waves can be further largely increased by tapering laterally the waveguide system. The approach for trapping microwaves has promising applications in magnetic sensing and magnetic non-linearity. [ABSTRACT FROM AUTHOR]