Attention-based generative adversarial networks improve prognostic outcome prediction of cancer from multimodal data.

The prediction of prognostic outcome is critical for the development of efficient cancer therapeutics and potential personalized medicine. However, due to the heterogeneity and diversity of multimodal data of cancer, data integration and feature selection remain a challenge for prognostic outcome prediction. We proposed a deep learning method with generative adversarial network based on sequential channel-spatial attention modules (CSAM-GAN), a multimodal data integration and feature selection approach, for accomplishing prognostic stratification tasks in cancer. Sequential channel-spatial attention modules equipped with an encoder-decoder are applied for the input features of multimodal data to accurately refine selected features. A discriminator network was proposed to make the generator and discriminator learning in an adversarial way to accurately describe the complex heterogeneous information of multiple modal data. We conducted extensive experiments with various feature selection and classification methods and confirmed that the CSAM-GAN via the multilayer deep neural network (DNN) classifier outperformed these baseline methods on two different multimodal data sets with miRNA expression, mRNA expression and histopathological image data: lower-grade glioma and kidney renal clear cell carcinoma. The CSAM-GAN via the multilayer DNN classifier bridges the gap between heterogenous multimodal data and prognostic outcome prediction.

Pipelined biomedical event extraction rivaling joint learning.

Biomedical event extraction is an information extraction task to obtain events from biomedical text, whose targets include the type, the trigger, and the respective arguments involved in an event. Traditional biomedical event extraction usually adopts a pipelined approach, which contains trigger identification, argument role recognition, and finally event construction either using specific rules or by machine learning. In this paper, we propose an n-ary relation extraction method based on the BERT pre-training model to construct Binding events, in order to capture the semantic information about an event's context and its participants. The experimental results show that our method achieves promising results on the GE11 and GE13 corpora of the BioNLP shared task with F1 scores of 63.14% and 59.40%, respectively. It demonstrates that by significantly improving the performance of Binding events, the overall performance of the pipelined event extraction approach or even exceeds those of current joint learning methods.

gutMDisorder v2.0: a comprehensive database for dysbiosis of gut microbiota in phenotypes and interventions.

Gut microbiota plays a significant role in maintaining host health, and conversely, disorders potentially lead to dysbiosis, an imbalance in the composition of the gut microbial community. Intervention approaches, such as medications, diets, and several others, also alter the gut microbiota in either a beneficial or harmful direction. In 2020, the gutMDisorder was developed to facilitate researchers in the investigation of dysbiosis of gut microbes as occurs in various disorders as well as with therapeutic interventions. The database has been updated this year, following revision of previous publications and newly published reports to manually integrate confirmed associations under multitudinous conditions. Additionally, the microbial contents of downloaded gut microbial raw sequencing data were annotated, the metadata of the corresponding hosts were manually curated, and the interactive charts were developed to enhance visualization. The improvements have assembled into gutMDisorder v2.0, a more advanced search engine and an upgraded web interface, which can be freely accessed via http://bio-annotation.cn/gutMDisorder/.

Characterization and role of collagen gene expressing hepatic cells following partial hepatectomy in mice.

BACKGROUND AND AIMS: The mechanism underlying liver regeneration following partial hepatectomy (PH) is not fully elucidated. We aimed to characterize collagen gene expressing hepatic cells following PH and examine their contribution to liver regeneration. APPROACH AND RESULTS: Col-GFP mice, which express GFP under the control of the collagen gene promoter, were used to detect collagen gene expressing cells following PH. The GFP-expressing cells were analyzed via single-cell RNA sequencing (scRNA-seq). Additionally, Col-ER Cre/RFP and Col-ER Cre/DTA mice were utilized to examine the cell fates and functional roles of collagen gene expressing cells in liver regeneration, respectively. The number of collagen gene expressing cells was found to be increased on day 3 and subsequently decreased on day 7 following PH. ScRNA-seq analysis of sorted collagen gene expressing cells showed that the regenerating liver was characterized by three distinct hepatic stellate cell (HSC) clusters, including one representing classic myofibroblasts. The other HSC clusters included an intermediately activated HSC cluster and a proliferating HSC cluster. Of these, the latter cluster was absent in the CCl 4 -induced liver fibrosis model. Cell fate tracing analysis using Col-ER Cre/RFP mice demonstrated that the collagen gene expressing cells escaped death during regeneration and remained in an inactivated state in the liver. Further, depletion of these cells using Col-ER Cre/DTA mice resulted in impaired liver regeneration. CONCLUSIONS: Heterogeneous HSC clusters, one of which was a unique proliferating cluster, were found to appear in the liver following PH. Collagen gene expressing cells, including HSCs, were found to promote liver regeneration.

Diastereoselective Synthesis of Pyrroloquinolines via N-H Functionalization of Indoles with Vinyl Sulfonium Salts.

A [2 + 4]/[1 + 2] annulation approach was successfully established to construct pyrroloquinoline-fused cyclopropane in a highly diastereoselective fashion (>20:1 dr). The tetracyclic 1,7-fused indoles were efficiently obtained from readily available starting materials under mild conditions. This methodology displays impressive substrate generality with two reaction components. The products resulting from this doubly annulative strategy are useful synthetic intermediates.

Synthesis of gem-Difluorohomoallyl Amines via a Transition-Metal-Free Defluorinative Alkylation of Benzyl Amines with Trifluoromethyl Alkenes.

A mild and transition-metal-free defluorinative alkylation of benzyl amines with trifluoromethyl alkenes is reported. The features of this protocol are easy-to-obtain starting materials, a wide range of substrates, and functional group tolerance as well as high atom economy, thus offering a strategy to access a variety of gem-difluorohomoallyl amines, which are extensively distributed in pharmaceuticals and bioactive agents, with excellent chemoselectivity. The primary products can be further transformed to a diversity of 2-fluorinated pyrroline compounds.

Generation of sulfones utilizing ß-sulfinyl esters as masked aryl sulfinates under redox-neutral conditions.

A method for generation of SVI sulfones from ß-sulfinyl esters (SIV) under transition-metal-free non-oxidative mild conditions is presented. Various sulfones have been achieved with moderate to excellent yields. The advantage of using ß-sulfinyl esters as masked aryl sulfinates has also been exemplified using brominated substrates. Oxygen isotope-labeling experiments indicated that the oxygen atoms incorporated into the sulfone product come from the sulfoxide of the ß-sulfinyl ester. Successive ß-elimination/O-addition/sulfinate esterification/ß-elimination processes are proposed for the mechanism of generating SVI from SIV.

High expression of autotaxin is associated with poor recurrence-free survival in cholangiocarcinoma.

BACKGROUND AND AIM: Autotaxin (ATX) is an extracellular lysophospholipase D that catalyzes the hydrolysis of lysophosphatidylcholine into lysophosphatidic acid (LPA). Recent accumulating evidence indicates the biological roles of ATX in malignant tumors. However, the expression and clinical implications of ATX in human cholangiocarcinoma (CCA) remain elusive. METHODS: In this study, the expression of ATX in 97 human CCA tissues was evaluated by immunohistochemistry. Serum ATX levels were determined in CCA patients (n = 26) and healthy subjects (n = 8). Autotaxin expression in cell types within the tumor microenvironment was characterized by immunofluorescence staining. RESULTS: High ATX expression in CCA tissue was significantly associated with a higher frequency of lymph node metastasis (p = 0.050). High ATX expression was correlated with shorter overall survival (p = 0.032) and recurrence-free survival (RFS) (p = 0.001) than low ATX expression. In multivariate Cox analysis, high ATX expression (p = 0.019) was an independent factor for shorter RFS. Compared with low ATX expression, high ATX expression was significantly associated with higher Ki-67-positive cell counts (p < 0.001). Serum ATX levels were significantly higher in male CCA patients than in healthy male subjects (p = 0.030). In the tumor microenvironment of CCA, ATX protein was predominantly expressed in tumor cells, cancer-associated fibroblasts, plasma cells, and biliary epithelial cells. CONCLUSIONS: Our study highlights the clinical evidence and independent prognostic value of ATX in human CCA.

Characterization and immunological effect of outer membrane vesicles from Pasteurella multocida on macrophages.

Pasteurella multocida is an important bacterial pathogen that can cause diseases in both animals and humans. Its elevated morbidity and mortality rates in animals result in substantial economic repercussions within the livestock industry. The prevention of diseases caused by P. multocida through immunization is impeded by the absence of a safe and effective vaccine. Outer membrane vesicles (OMVs) secreted from the outer membrane of Gram-negative bacteria are spherical vesicular structures that encompass an array of periplasmic components in conjunction with a diverse assortment of lipids and proteins. These vesicles can induce antibacterial immune responses within the host. P. multocida has been shown to produce OMVs. Nonetheless, the precise characteristics and immunomodulatory functions of P. multocida OMVs have not been fully elucidated. In this study, OMVs were isolated from P. multocida using an ultrafiltration concentration technique, and their morphology, protein constitution, and immunomodulatory properties in RAW264.7 cells were studied. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) revealed that the OMVs exhibited typical spherical and bilayered lipid vesicular architecture, exhibiting an average diameter of approximately 147.5 nm. The yield of OMVs was 2.6 × 1011 particles/mL. Proteomic analysis revealed a high abundance of membrane-associated proteins within P. multocida OMVs, with the capability to instigate the host's immune response. Furthermore, OMVs stimulated the proliferation and cellular uptake of macrophages and triggered the secretion of cytokines, such as TNF-ɑ, IL-1ß, IL-6, IL-10, and TGF-ß1. Consequently, our results indicated that OMVs from P. multocida could directly interact with macrophages and regulate their immune function in vitro. These results supported the prospective applicability of P. multocida OMVs as a platform in the context of vaccine development. KEY POINTS: • Preparation and characterization of P. multocida OMVs. • P. multocida OMVs possess a range of antigens and lipoproteins associated with the activation of the immune system. • P. multocida OMVs can activate the proliferation, internalization, and cytokine secretion of macrophages in vitro.

Screening indicators to evaluate the clinical significance of drug-drug interactions in polypharmacy among older adults with psychiatric disorders: a delphi study.

BACKGROUND: Polypharmacy is common in older adults with psychiatric disorders, but no consensus has reached about the reliable indicators evaluating the benefits and risks of drug-drug interactions (DDIs) in polypharmacy. We aimed to identify indicators suitable for evaluating the clinical significance of DDIs in polypharmacy in older adults with psychiatric disorders. METHODS: The online tools were used to distribute and collect the questionnaires. The Delphi method was applied to analyze experts' opinions. The degree of authority and coordination of experts were analyzed using the coefficient of variation, coefficient of coordination, expert's judgment factor, familiarity with the study content factor, and Kendall coordination coefficient. Statistical analysis was conducted using the IBM SPSS® Statistics Package version 26.0. RESULTS: After three rounds of expert consultation, five primary and eleven secondary indicators were identified. The primary "pharmacodynamic indicator" included "severity of adverse drug reactions", "duration of adverse drug reaction", "symptom relief", "time to onset of symptomatic relief", "number of days in hospital", and "duration of medication". The secondary "pharmacokinetic indicator" contained "dosage administered" and "dosing intervals". The primary "patient tolerance indicator" contained one secondary indicator of "patient tolerability". The primary indicator "patient adherence" contained one secondary indicator of "patient adherence to medication". The primary indicator "cost of drug combination" contained one secondary indicator of "readmission". These indicators were used to determine the clinical significance of DDIs during polypharmacy. CONCLUSIONS: The clinical significance of drug combinations should be taken into account when polypharmacy is used in the elderly. The five primary indicators and eleven secondary indicators might be preferred to evaluate their risks and benefits. Medication management in this population requires a multidisciplinary team, in which nurses play a key role. Future research should focus on how to establish efficient multidisciplinary team workflows and use functional factors to assess DDIs in polypharmacy for psychiatric disorders.

Association of dietary glycemic index and glycemic load with the risk of gestational diabetes mellitus: a systematic review and dose-response meta-analysis.

OBJECTIVE: To comprehensively assess the dose-response association between dietary glycemic index (GI) and glycemic load (GL) and gestational diabetes mellitus (GDM) risk. METHODS: PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP databases were searched up to May 29, 2024. Studies with at least three exposure categories were included. Dose-response analysis was also performed when covariates were adjusted in the included studies. RESULTS: Thirteen studies involving 39,720 pregnant women were included. A linear relationship was found between GI and the risk of GDM (χ2 = 4.77, Pnon-linearity = .0923). However, association was not significant (χ2 = 0.06, p = .8000). For every unit increase in GI (range 0-30), GDM risk increased by 0.29%. After adjusting for covariates, the linear relationship persisted (χ2 = 4.95, Pnon-linearity = .084) with no significant association (χ2 = 0.08, p = .7775). For GL, a linear relationship was also found (χ2 = 4.17, Pnon-linearity =.1245), but GL was not significantly associated with GDM risk (χ2 = 2.63, p = .1049). The risk of GDM increased by 0.63% per unit increase in GL. After covariate adjustment, a significant association was observed (χ2 = 6.28, p = .0122). CONCLUSION: No significant association between GI and GDM risk was found. After adjusting for covariates, GL shows a significant association with GDM risk. Our findings emphasize the importance of considering dietary GL in managing the risk of GDM. Future research should continue to explore these relationships with standardized diagnostic criteria and robust adjustment for potential confounders.

Environmental levels of azoxystrobin disturb male zebrafish behavior: Possible roles of oxidative stress, cholinergic system, and dopaminergic system.

A widely applied pesticide of azoxystrobin, is increasingly detected in the water environment. Concern has been raised against its potential detriment to aquatic ecosystems. It has been shown that exposure to azoxystrobin interfere with the locomotor behavior of zebrafish larvae. This study aims to investigate whether exposure to environmental levels of azoxystrobin (2 µg/L, 20 µg/L, and 200 µg/L) changes the behavior of male adult zebrafish. Herein, we evaluated behavioral response (locomotor, anxiety-like, and exploratory behaviors), histopathology, biochemical indicators, and gene expression in male adult zebrafish upon azoxystrobin exposure. The study showed that exposure to azoxystrobin for 42 days remarkably increased the locomotor ability of male zebrafish, resulted in anxiety-like behavior, and inhibited exploratory behavior. After treatment with 200 µg/L azoxystrobin, vasodilatation, and congestion were observed in male zebrafish brains. Exposure to 200 µg/L azoxystrobin notably elevated ROS level, MDA concentration, CAT activity, and AChE activity, while inhibiting SOD activity, GPx activity, ACh concentration, and DA concentration in male zebrafish brains. Moreover, the expression levels of genes related to the antioxidant, cholinergic, and dopaminergic systems were significantly changed. This suggests that azoxystrobin may interfere with the homeostasis of neurotransmitters by causing oxidative stress in male zebrafish brains, thus affecting the behavioral response of male zebrafish.

Do Habitat MRI and Fractal Analysis Help Distinguish Triple-Negative Breast Cancer From Non-Triple-Negative Breast Carcinoma.

Purpose: To determine whether multiparametric MRI-based spatial habitats and fractal analysis can help distinguish triple-negative breast cancer (TNBC) from non-TNBC. Method: Multiparametric DWI and DCE-MRI at 3T were obtained from 142 biopsy- and surgery-proven breast cancer with 148 breast lesions (TNBC = 26 and non-TNBC = 122). The contrast-enhancing lesions were divided into 3 spatial habitats based on perfusion and diffusion patterns using K-means clustering. The fractal dimension (FD) of the tumour subregions was calculated. The accuracy of the habitat segmentation was measured using the Dice index. Inter- and intra-reader reliability were evaluated with the intraclass correlation coefficient (ICC). The ability to predict TNBC status was assessed using the receiver operating characteristic curve. Results: The Dice index for the whole tumour was 0.81 for inter-reader and 0.88 for intra-reader reliability. The inter- and intra-reader reliability were excellent for all 3 tumour habitats and fractal features (ICC > 0.9). TNBC had a lower hypervascular cellular habitat and higher FD 1 compared to non-TNBC (all P < .001). Multivariate analysis confirmed that hypervascular cellular habitat (OR = 0.88) and FD 1 (OR = 1.35) were independently associated with TNBC (all P < .001) after adjusting for rim enhancement, axillary lymph nodes status, and histological grade. The diagnostic model combining hypervascular cellular habitat and FD 1 showed excellent discriminatory ability for TNBC, with an AUC of 0.951 and an accuracy of 91.9%. Conclusions: The fraction of hypervascular cellular habitat and its FD may serve as useful imaging biomarkers for predicting TNBC status.

FUNDC1 modulates mitochondrial defects and pancreatic ß-cell dysfunction under lipotoxicity.

Insulin resistance and many metabolic disorders are causally linked to mitochondrial dysfunction or defective mitochondrial quality control. Mitophagy is a highly selective mechanism that recognizes and removes damaged mitochondria to maintain mitochondrial homeostasis. Here, we addressed the potential role of FUNDC1, a mediator of mitophagy, in pancreatic ß-cell dysfunction under lipotoxicity. In pancreatic MIN6 cells, FUNDC1 deficiency aggravated palmitate-induced mitochondrial dysfunction, which led to cell death and insulin insensitivity. Interestingly, FUNDC1 overexpression prevented these cellular harms brought on by palmitate. In mice models, pancreatic-specific FUNDC1 overexpression alleviated high-fat diet (HFD)-induced insulin resistance and obesity. Mechanistically, pancreatic-specific overexpression of FUNDC1 ameliorated mitochondrial defects and endoplasmic reticulum (ER) stress upon HFD. Our research indicates that FUNDC1 plays an essential role in apoptosis and dysfunction of pancreatic ß-cells via modulating lipotoxicity-induced mitochondrial defects.

Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.

Antitumor activity of pegylated human interferon ß as monotherapy or in combination with immune checkpoint inhibitors via tumor growth inhibition and dendritic cell activation.

Type I interferons (IFN), especially human IFN alpha (IFNα), have been utilized for antitumor therapy for decades. Human interferon beta (IFNß) is rarely used for cancer treatment, despite advantages over IFNα in biological activities such as tumor growth inhibition and dendritic cell (DC) activation. The utilization of pegylated human IFNß (PEG-IFNß), as monotherapy or in combination with immune checkpoint inhibitors (ICIs) was evaluated in this study through in vivo efficacy studies in syngeneic mouse melanoma, non-small cell lung cancer (NSCLC), and colon adenocarcinoma (COAD) models resistant to immune checkpoint inhibitors (ICIs). In vitro comparative study of PEG-IFNß and pegylated IFNα-2b was performed in terms of tumor growth inhibition against human melanoma, NSCLC and COAD cell lines and activation of human monocyte-derived DCs (MoDCs). Our data demonstrate that the in vivo antitumor effects of PEG-IFNß are partially attributable to tumor growth-inhibitory effects and DC-activating activities, superior to pegylated IFNα-2b. Our findings suggest that utilizing PEG-IFNß as an antitumor therapy can enhance the therapeutic effect of ICIs in ICI-resistant tumors by directly inhibiting tumor growth and induction of DC maturation.

Validation of Luminex immunological and competitive Luminex immunological assays for clinical immunogenicity assessment of a 14-valent recombinant human papillomavirus vaccine.

A novel virus-like particle (VLP)-based multivalent recombinant human papillomavirus (HPV) vaccine was developed and evaluated in human, including 14 HPV-type specific VLP antigens (HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). The pseudovirus-based neutralizing assay (PBNA) method is widely used for immunogenicity assessment of HPV vaccine in clinical trials. However, as many as 14 antigen-specific antibody levels need be determined, PBNA is, for many reasons, challenging and time-consuming. In this study, we developed a Luminex immunological assay (LIA) and a competitive Luminex immunological assay (cLIA). These methods increase the throughput, reproducibility and precision, as well as reduce the complexity. All assay parameters showed good characteristics in the validation of both methods, benefiting from highly purified and structurally correct VLPs, high specific antibodies, standard VLP-microspheres and PE-mAbs conjugating process, adequate assay development and stable system. Validation data support the use of both methods for immunogenicity assessment in clinical trials. LIA showed higher sensitivity than cLIA, and due to limited epitopes of mAb, cLIA detected lower antibody responses, and therefore, fewer antibodies. This work not only supports clinical trials of 14-valent HPV vaccines more efficiently and reliably, but also provides a set of validation strategies and usable standards for general vaccine immunogenicity testing.

CycC1;1 negatively modulates ABA signaling by interacting with and inhibiting ABI5 during seed germination.

Regulation of seed germination is important for plant survival and propagation. ABSCISIC ACID (ABA) INSENSITIVE5 (ABI5), the central transcription factor in the ABA signaling pathway, plays a fundamental role in the regulation of ABA-responsive gene expression during seed germination; however, how ABI5 transcriptional activation activity is regulated remains to be elucidated. Here, we report that C-type Cyclin1;1 (CycC1;1) is an ABI5-interacting partner affecting the ABA response and seed germination in Arabidopsis (Arabidopsis thaliana). The CycC1;1 loss-of-function mutant is hypersensitive to ABA, and this phenotype was rescued by mutation of ABI5. Moreover, CycC1;1 suppresses ABI5 transcriptional activation activity for ABI5-targeted genes including ABI5 itself by occupying their promoters and disrupting RNA polymerase II recruitment; thus the cycc1;1 mutant shows increased expression of ABI5 and genes downstream of ABI5. Furthermore, ABA reduces the interaction between CycC1;1 and ABI5, while phospho-mimic but not phospho-dead mutation of serine-42 in ABI5 abolishes CycC1;1 interaction with ABI5 and relieves CycC1;1 inhibition of ABI5-mediated transcriptional activation of downstream target genes. Together, our study illustrates that CycC1;1 negatively modulates the ABA response by interacting with and inhibiting ABI5, while ABA relieves the CycC1;1 interaction with and inhibition of ABI5 to activate ABI5 activity for the ABA response, thereby inhibiting seed germination.

Enhancing harmonic brightness near the cutoff region by using laser pulses with a small positive chirp.

Efficient enhancement of harmonic brightness near the cutoff region is achieved by employing laser pulses with a small positive chirp in theory, where the laser intensity and frequency near the peak of the laser pulse are almost unchanged relative to the chirp-free field. The improvement of harmonic brightness is achieved under the condition that the ionization probability is almost unchanged. Through the analysis of the harmonics contributed by the rising and falling parts of the laser pulse, we have uncovered a "frequency compensation" mechanism that leads to an enhanced harmonic brightness near the cutoff region. Under appropriate chirp parameters, the harmonics contributed by the rising and falling parts can be constructively interfered in a smaller frequency range with greater intensity, thereby obtaining harmonics with good monochromaticity and high brightness. This study explains the mechanism of harmonic brightness enhancement from a new perspective, and provides a new idea for harmonic regulation without changing the ionization.

Genetic mapping of the wheat leaf rust resistance gene Lr19 and development of translocation lines to break its linkage with yellow pigment.

KEY MESSAGE: The leaf rust resistance gene Lr19, which is present on the long arm of chromosome 7E1 in Thinopyrum ponticum, was mapped within a 0.3-cM genetic interval, and translocation lines were developed to break its linkage with yellow pigmentation The leaf rust resistance locus Lr19, which was transferred to wheat (Triticum aestivum) from its relative Thinopyrum ponticum in 1966, still confers broad resistance to most known races of the leaf rust pathogen Puccinia triticina (Pt) worldwide. However, this gene has not previously been fine-mapped, and its tight linkage with a gene causing yellow pigmentation has limited its application in bread wheat breeding. In this study, we genetically mapped Lr19 using a bi-parental population from a cross of two wheat-Th. ponticum substitution lines, the Lr19-carrying line 7E1(7D) and the leaf rust-susceptible line 7E2(7D). Genetic analysis of the F2 population and the F2:3 families showed that Lr19 was a single dominant gene. Genetic markers allowed the gene to be mapped within a 0.3-cM interval on the long arm of Th. ponticum chromosome 7E1, flanked by markers XsdauK3734 and XsdauK2839. To reduce the size of the Th. ponticum chromosome segment carrying Lr19, the Chinese Spring Ph1b mutant was employed to promote recombination between the homoeologous chromosomes of the wheat chromosome 7D and the Th. ponticum chromosome 7E1. Two translocation lines with short Th. ponticum chromosome fragments carrying Lr19 were identified using the genetic markers closely linked to Lr19. Both translocation lines were resistant to 16 Pt races collected throughout China. Importantly, the linkage between Lr19 and yellow pigment content was broken in one of the lines. Thus, the Lr19 linked markers and translocation lines developed in this study are valuable resources in marker-assisted selection as part of common wheat breeding programs.