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OBJECTIVE: To quantitatively analyze the morphological characteristics of osteophytes in DISH and syndesmophytes in AS, and summarize different ossification patterns to help identify the two diseases. Associated factors for new bone formation would be investigated. METHODS: Fifty patients with DISH and 50 age-, sex-, CT examination site- matched patients with AS were enrolled. Radiographic and clinical data were reviewed. Osteophytes (syndesmophytes) in front of each vertebral body and the corresponding intervertebral disc space were defined as vertebral osteophytes unit (VOU). The volume, angle and location (contralateral, ipsilateral, bilateral) of osteophytes in each VOU were measured and compared between DISH and AS groups. RESULTS: In each VOU, the volume and angle of osteophytes in DISH were significantly larger. The best osteophytes volume and angle cutoff value in predicting DISH was 0.59 cm3 and 40.15°. Contralateral, bilateral, ipsilateral osteophytes were recorded in 59.32%, 36.38%, 4.3% of assessed VOUs in patients with DISH and 64.78%, 29.31%, 5.91% in AS (p<0.001), respectively. As to ipsilateral osteophytes, the volume was inversely correlated with the center of the vertebral body to the center of the descending aorta (DISH: r = -0.45, p= 0.01; AS: r = -0.83, p<0.001). Advanced age, disease duration, smoking and overweight contribute to the progression of osteophytes and syndesmophytes. CONCLUSION: Morphological features of osteophytes are helpful to distinguish DISH with AS. Aortic pulsations inhibit or hinder new bone formation in both DISH and AS. Maintaining normal BMI could postpone osteophytes formation.
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KEY MESSAGE: Major QTL for grain number per spike were identified on chromosomes 2B and 2D. Haplotypes and candidate genes of QGns.cib-2B.1 were analyzed. Grain number per spike (GNS) is one of the main components of wheat yield. Genetic dissection of their regulatory factors is essential to improve the yield potential. In present study, a recombinant inbred line population comprising 180 lines developed from the cross between a high GNS line W7268 and a cultivar Chuanyu12 was employed to identify quantitative trait loci (QTL) associated with GNS across six environments. Two major QTL, QGns.cib-2B.1 and QGns.cib-2D.1, were detected in at least four environments with the phenotypic variations of 12.99-27.07% and 8.50-13.79%, respectively. And significant interactions were observed between the two major QTL. In addition, QGns.cib-2B.1 is a QTL cluster for GNS, grain number per spikelet and fertile tiller number, and they were validated in different genetic backgrounds using Kompetitive Allele Specific PCR (KASP) markers. QGns.cib-2B.1 showed pleotropic effects on other yield-related traits including plant height, spike length, and spikelet number per spike, but did not significantly affect thousand grain weight which suggested that it might be potentially applicable in breeding program. Comparison analysis suggested that QGns.cib-2B.1 might be a novel QTL. Furthermore, haplotype analysis of QGns.cib-2B.1 indicated that it is a hot spot of artificial selection during wheat improvement. Based on the expression patterns, gene annotation, orthologs analysis and sequence variations, the candidate genes of QGns.cib-2B.1 were predicted. Collectively, the major QTL and KASP markers reported here provided a wealth of information for the genetic basis of GNS and grain yield improvement.
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Mapeo Cromosómico , Cromosomas de las Plantas , Haplotipos , Fenotipo , Sitios de Carácter Cuantitativo , Triticum , Triticum/genética , Triticum/crecimiento & desarrollo , Cromosomas de las Plantas/genética , Mapeo Cromosómico/métodos , Marcadores Genéticos , Grano Comestible/genética , Grano Comestible/crecimiento & desarrollo , Semillas/crecimiento & desarrollo , Semillas/genética , Fitomejoramiento , Alelos , Genes de PlantasRESUMEN
KEY MESSAGE: A major and stable QTL for fertile spikelet number per spike and grain number per fertile spikelet identified in a 4.96-Mb interval on chromosome 2A was validated in different genetic backgrounds. Fertile spikelet number per spike (FSN) and grain number per fertile spikelet (GNFS) contribute greatly to wheat yield improvement. To detect quantitative trait loci (QTL) associated with FSN and GNFS, we used a recombinant inbred line population crossed by Zhongkemai 13F10 and Chuanmai 42 in eight environments. Two Genomic regions associated with FSN were detected on chromosomes 2A and 6A using bulked segregant exome sequencing analysis. After the genetic linkage maps were constructed, four QTL QFsn.cib-2A, QFsn.cib-6A, QGnfs.cib-2A and QGnfs.cib-6A were identified in three or more environments. Among them, two major QTL QFsn.cib-2A (LOD = 4.67-9.34, PVE = 6.66-13.05%) and QGnfs.cib-2A (LOD = 5.27-11.68, PVE = 7.95-16.71%) were detected in seven and six environments, respectively. They were co-located in the same region, namely QFsn/Gnfs.cib-2A. The developed linked Kompetitive Allele Specific PCR (KASP) markers further validated this QTL in a different genetic background. QFsn/Gnfs.cib-2A showed pleiotropic effects on grain number per spike (GNS) and spike compactness (SC), and had no effect on grain weight. Since QFsn/Gnfs.cib-2A might be a new locus, it and the developed KASP markers can be used in wheat breeding. According to haplotype analysis, QFsn/Gnfs.cib-2A was identified as a target of artificial selection during wheat improvement. Based on haplotype analysis, sequence differences, spatiotemporal expression patterns, and gene annotation, the potential candidate genes for QFsn/Gnfs.cib-2A were predicted. These results provide valuable information for fine mapping and cloning gene(s) underlying QFsn/Gnfs.cib-2A.
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Sitios de Carácter Cuantitativo , Triticum , Triticum/genética , Mapeo Cromosómico , Fitomejoramiento , Pan , Fenotipo , Grano Comestible/genéticaRESUMEN
Enthesitis, a characteristic of spondyloarthritis, has been paid considerable attention by researchers, and numerous enthesitis-related studies have been published in recent years. However, no study has been conducted to analyze enthesitis-related researches with bibliometric methods. This study aimed to provide a broad understanding of enthesitis-related researches and explore the direction of hot topics and future research trends from a bibliometric perspective. The global literatures on enthesitis published from 2012 to 2021 were scanned in the Web of Science Core Collection databases. Visualization and bibliometric analyses were generated by an online bibliometric platform and VOSviewer software to explore the hot topics and research trends. A total of 1,181 documents were included in this study. Publications were mainly from these countries in North America and Western Europe. Among these countries, the United States was the leading country with the maximum publication counts (210), highest h-index (47), and largest collaboration network as of June 29, 2022. The most influential journal and powerful author were Journal of Rheumatology and Professor Mease PJ, respectively. Co-occurrence analysis of keywords identified that "axial spondyloarthritis", "interleukin 23", and "secukinumab" might be the future hotspots. More and more attention had been paid to enthesitis in the past 10 years. Present studies focused on the effect of inflammatory cytokines involved in the pathogenesis and the development of antibodies against these factors. These studies played a key role in understanding the research direction and subsequent management of enthesitis, and helped researchers extract hidden valuable information for further study.
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Bibliometría , Entesopatía , Espondiloartritis , Humanos , Citocinas , Bases de Datos Factuales , PublicacionesRESUMEN
Spike length (SL) is the key determinant of plant architecture and yield potential. In this study, 193 recombinant inbred lines (RILs) derived from a cross between 13F10 and Chuanmai 42 (CM42) were evaluated for spike length in six environments. Sixty RILs consisting of 30 high and 30 low SLs were genotyped using the bulked segregant analysis exome sequencing (BSE-Seq) analysis for preliminary quantitative trait locus (QTL) mapping. A 6.69 Mb (518.43-525.12 Mb) region on chromosome 5AL was found to have a significant effect on the SL trait. Fifteen competitive allele-specific PCR (KASP) markers were successfully converted from the single nucleotide polymorphisms (SNPs) in the SL target region. Combined with four novel simple sequence repeat (SSR) markers, a genetic linkage map spanning 21.159 cM was constructed. The mapping result confirmed the identity of a major and stable QTL named QSl.cib-5A in the targeted region that explained 7.88-26.60% of the phenotypic variation in SL. QSl.cib-5A was narrowed to a region of 4.84 cM interval corresponding to a 4.67 Mb (516.60-521.27 Mb) physical region in the Chinese Spring RefSeq v2.0 containing 17 high-confidence genes with 25 transcripts. In addition, this QTL exhibited pleiotropic effects on spikelet density (SD), with the phenotypic variances proportion ranging from 11.34 to 19.92%. This study provides a foundational step for cloning the QSl.cib-5A, which is involved in the regulation of spike morphology in common wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01249-6.
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OBJECTIVE: To identify clinical and pathological differences between IgG4-related retroperitoneal fibrosis (IgG4-RPF) and idiopathic RPF (iRPF) in a Chinese population. METHOD: Clinical and pathological data of 50 RPF patients from 2006 to 2016 were retrospectively analysed. The presence of at least one characteristic histopathological feature, >30 IgG4+ plasma cells per high power field, and an IgG4+/IgG+ plasma cells ratio cutoff of >40% were used to define IgG4-RPF. RESULTS: Patients with IgG4-RPF were significantly more likely to have pain (94.1 vs 68.8%, P = 0.048), elevated serum IgE concentration (166.1 vs 40.2 IU/ml, P = 0.029) and tissue eosinophilia (47.1 vs 12.5%, P = 0.018), compared with patients with iRPF. In the IgG4-RPF subgroup, patients with tissue eosinophilia demonstrated higher levels of CRP (4.3 vs 1.9 mg/dl, P = 0.027) and ESR (62.1 vs 22.8 mm/h, P = 0.001). Among the 50 patients with RPF, the average number of tissue IgG4+ plasma cells was positively correlated with the number of tissue eosinophils (r = 0.37, P = 0.009). Moreover, serum IgG4 concentration and serum IgE concentration showed positive correlation (r = 0.834, P = 0.000). CONCLUSION: The distinct serological and histopathological features of Chinese patients with IgG4-RPF were elevated serum IgE concentration and tissue eosinophilia, which potentially can aid and support the diagnosis. As serum IgG4 concentration may be normal in patients with IgG4-RPF, serum IgE may represent a useful serological marker in distinguishing IgG4-RPF from iRPF.
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Inmunoglobulina G/sangre , Células Plasmáticas/inmunología , Fibrosis Retroperitoneal/inmunología , Adolescente , Adulto , Anciano , Niño , China , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Fibrosis Retroperitoneal/sangre , Estudios Retrospectivos , Adulto JovenRESUMEN
Objective:To analyze the clinical feature, diagnosis and treatment of Anca-associated vasculitis with ear symptoms. Methods:In this retrospective study, we summarized the clinical and laboratory examination, pure tone audiometry, aural immittance measurement, CT scan of temporal bone and treatment of 40 patients in the First Medical Center of the PLA General Hospital. Results:A total of 11 casesï¼27.5%ï¼ had the initial symptom in the ear. The most common symptoms were hearing loss, and the other symptoms included a sense of ear fullness, otorrhea and tinnitus. There were 35 cases with hearing loss: 19 cases with conductive hearing lossï¼47.5%ï¼, 9 cases with sensorineural hearing lossï¼22.5%ï¼, and 7 cases with mixed hearing lossï¼17.5%ï¼. 5 cases had a sense of ear fullness or tinnitus, and the results of the hearing test were normalï¼12.5%ï¼. All of the 40 patients had multi-system involvement, and respiratory system accounted for the most. All patients had a positive result of Anti-neutrophil cytoplasmic antibodyï¼ANCAï¼. Treatment included systemic hormonal, immunosuppressive, or biologic therapy. There were 3 cases recoveredï¼7.5%ï¼, 22 cases with alleviated ear symptomsï¼55.0%ï¼, 6 cases with recurrent hearing lossï¼15%ï¼ and 9 cases had no significant improvementï¼22.5%ï¼. Conclusion:Conductive deafnessï¼secretory otitis mediaï¼ can be the first manifestation in the early stage of otitis media with AAVï¼OMAAVï¼, later it may turn to binaural mixed deafness. Otolaryngologists need to consider OMAAV diagnosis when diagnosing and treating patients with recurrent secretory otitis media. Multi-system symptom consultation and ANCA examination can help identify. Early systemic medication and the application of immunosuppressants or biological agents can help relieve the ear symptoms.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Sordera , Otitis Media con Derrame , Acúfeno , Humanos , Anticuerpos Anticitoplasma de Neutrófilos , Estudios Retrospectivos , Pérdida Auditiva Conductiva , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Audiometría de Tonos PurosRESUMEN
Grain hardness (Gh) is important for wheat processing and end-product quality. Puroindolines polymorphism explains over 60% of Gh variation and the novel genetic factors remain to be exploited. In this study, a total of 153 quantitative trait loci (QTLs), clustered into 12 genomic intervals (C1-C12), for 13 quality-related traits were identified using a recombinant inbred line population derived from the cross of Zhongkemai138 (ZKM138) and Chuanmai44 (CM44). Among them, C7 (harboring eight QTLs for different quality-related traits) and C8 (mainly harboring QGh.cib-5D.1 for Gh) were attributed to the famous genes, Rht-D1 and Pina, respectively, indicating that the correlation of involved traits was supported by the pleotropic or linked genes. Notably, a novel major stable QTL for Gh was detected in the C12, QGh.cib-7D, with ZKM138-derived allele increasing grain hardness, which was simultaneously mapped by the BSE-Seq method. The geographic pattern and transmissibility of this locus revealed that the increasing-Gh allele is highly frequently present in 85.79% of 373 worldwide wheat varieties and presented 99.31% transmissibility in 144 ZKM138-derivatives, indicating the non-negative effect on yield performance and that its indirect passive selection has happened during the actual breeding process. Thus, the contribution of this new Gh-related locus was highlighted in consideration of improving the efficiency and accuracy of the soft/hard material selection in the molecular marker-assisted process. Further, TraesCS7D02G099400, TraesCS7D02G098000, and TraesCS7D02G099500 were initially deduced to be the most potential candidate genes of QGh.cib-7D. Collectively, this study provided valuable information of elucidating the genetic architecture of Gh for wheat quality improvement.
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BACKGROUND: Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. METHODS: Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. RESULTS: We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. CONCLUSION: Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.
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Linfocitos T CD4-Positivos , Metilación de ADN , Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Metilación de ADN/genética , Linfocitos T CD4-Positivos/metabolismo , Femenino , Masculino , Adulto , Nefritis Lúpica/genética , Lupus Eritematoso Sistémico/genética , Epigénesis Genética/genética , Islas de CpG/genética , Estudios de Casos y Controles , Persona de Mediana Edad , BiomarcadoresRESUMEN
The objectives of this study were to characterize dietary fiber (DF) intake in patients with ankylosing spondylitis (AS), to assess whether DF intake affects disease activity in AS, and to investigate the effect of DF intake on disease activity in AS in the context of functional bowel disease (FBD) symptoms. We recruited 165 patients with AS and divided them into two groups according to whether they had a high DF intake > 25 g/d to investigate the characteristics of people with high DF intake. Some 72 of the 165 AS patients (43%) met the criteria for high DF intake, which was more common in patients with negative FBD symptoms (68%). Data analysis revealed that DF intake was negatively associated with AS disease activity and did not differ statistically significantly from FBD symptoms. Multivariate adjusted models were used to explore the effect of DF intake on AS disease activity. ASDAS-CRP and BASDAI were stable and negatively correlated across models in both groups with and without FBD symptoms. Thus, DF intake positively affected disease activity in patients with AS. ASDAS-CRP and BASDAI were negatively correlated with DF intake.
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Grain number per spike (GNS) is a crucial component of grain yield and plays a significant role in improving wheat yield. To identify quantitative trait loci (QTL) associated with GNS, a recombinant inbred line (RIL) population derived from the cross of Zhongkemai 13F10 and Chuanmai 42 was employed to conduct QTL mapping across eight environments. Based on the bulked segregant exome sequencing (BSE-Seq), genomic regions associated with GNS were detected on chromosomes 5A and 6A. According to the constructed genetic maps, two major QTL QGns.cib-5A (LOD = 4.35-8.16, PVE = 8.46-14.43%) and QGns.cib-6A (LOD = 3.82-30.80, PVE = 5.44-12.38%) were detected in five and four environments, respectively. QGns.cib-6A is a QTL cluster for other seven yield-related traits. QGns.cib-5A and QGns.cib-6A were further validated using linked Kompetitive Allele Specific PCR (KASP) markers in different genetic backgrounds. QGns.cib-5A exhibited pleiotropic effects on productive tiller number (PTN), spike length (SL), fertile spikelet number per spike (FSN), and ratio of grain length to grain width (GL/GW) but did not significantly affect thousand grain weight (TGW). Haplotype analysis revealed that QGns.cib-5A and QGns.cib-6A were the targets of artificial selection during wheat improvement. Candidate genes for QGns.cib-5A and QGns.cib-6A were predicted by analyzing gene annotation, spatiotemporal expression patterns, and orthologous and sequence differences. These findings will be valuable for fine mapping and map-based cloning of genes underlying QGns.cib-5A and QGns.cib-6A.
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OBJECTIVES: To explore the value of plasmablasts in predicting disease relapse in IgG4-related diseases (IgG4-RD). METHODS: Treatment-naïve IgG4-RD patients treated with glucocorticoid (GC) monotherapy or leflunomide (LEF) and GC combination therapy diagnosed at the Chinese PLA General Hospital during February 2017 and January 2018 were included in this study. The absolute plasmablast count was measured by using the absolute count tubes with flow cytometry. Patients were categorized into high and low plasmablast level groups by defining the median number of plasmablasts as the cut-off value. The characteristics of the clinical manifestations between the two groups were compared. In addition, the correlation of plasmablast count with other indicators and its clinical value in predicting disease relapse were evaluated. RESULTS: Data of 37 treatment-naïve IgG4-RD patients were analyzed. The median (IQR) absolute count of plasmablasts was 4.0 (2.8-7.5)/µL, which was correlated with the lymphocyte percentage, serum IgG, IgG4, and IgG4/IgG. The baseline absolute count of plasmablasts was an independent risk factor for disease relapse in IgG4-RD patients (HR, 1.199; 95% CI, 1.030-1.396, P = 0.019), and the application of LEF was an independent protective factor (HR, 0.283; 95% CI, 0.106-0.759, p = 0.012). CONCLUSIONS: The present study preliminarily indicated that baseline absolute plasmablast count may independently predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. More efforts are still needed to be performed in the future. Key Points ⢠The absolute count of plasmablasts is correlated with the lymphocyte percentage, serum IgG, IgG4 and IgG4/IgG. ⢠The baseline absolute plasmablast count may predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. ⢠The application of LEF is an independent protective factor for disease relapse in IgG4-RD.
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Enfermedad Relacionada con Inmunoglobulina G4 , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/tratamiento farmacológico , Células Plasmáticas , Leflunamida/uso terapéutico , Enfermedad Crónica , Recurrencia , Inmunoglobulina GRESUMEN
Mining novel and less utilized thousand grain weight (TGW) related genes are useful for improving wheat yield. In this study, a recombinant inbred line population from a cross between Zhongkemai 138 (ZKM138, high TGW) and Chuanmai 44 (CM44, low TGW) was used to construct a new Wheat 50K SNP array-derived genetic map that spanned 1,936.59 cM and contained 4, 139 markers. Based on this map, ninety-one quantitative trait loci (QTL) were detected for eight grain-related traits in six environments. Among 58 QTLs, whose superior alleles were contributed by ZKM138, QTgw.cib-6A was a noticeable major stable QTL and was also highlighted by bulked segregant analysis with RNA sequencing (BSR-Seq). It had a pyramiding effect on TGW enhancement but no significant trade-off effect on grain number per spike or tiller number, with two other QTLs (QTgw.cib-2A.2 and QTgw.cib-6D), possibly explaining the excellent grain performance of ZKM138. After comparison with known loci, QTgw.cib-6A was deduced to be a novel locus that differed from nearby TaGW2 and TaBT1. Seven simple sequence repeat (SSR) and thirty-nine kompetitive allele-specific PCR (KASP) markers were finally developed to narrow the candidate interval of QTgw.cib-6A to 4.1 Mb. Only six genes in this interval were regarded as the most likely candidate genes. QTgw.cib-6A was further validated in different genetic backgrounds and presented 88.6% transmissibility of the ZKM138-genotype and a 16.4% increase of TGW in ZKM138 derivatives. And the geographic pattern of this locus revealed that its superior allele is present in only 6.47% of 433 Chinese modern wheat varieties, indicating its potential contribution to further high-yield breeding.
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Spike compactness (SC) and length (SL) are the components of spike morphology and are strongly related to grain yield in wheat (Triticum aestivum L.). To investigate quantitative trait loci (QTL) associated with SC and SL, a recombinant inbred lines (RIL) population derived from the cross of Bailangmai (BLM, a Tibet landrace) and Chuanyu 20 (CY20, an improved variety) was employed in six environments. Three genomic regions responsible for SC and SL traits were identified on chromosomes 2A and 2D using bulked segregant exome sequencing (BSE-Seq). By constructing genetic maps, six major QTL were repeatedly detected in more than four environments and the best linear unbiased estimation (BLUE) datasets, explaining 7.00-28.56% of the phenotypic variation and the logarithm of the odd (LOD) score varying from 2.50 to 13.22. They were co-located on three loci, designed as QSc/Sl.cib-2AS, QSc/Sl.cib-2AL, and QSc/Sl.cib-2D, respectively. Based on the flanking markers, their interactions and effects on the corresponding trait and other agronomic traits were also analyzed. Comparison analysis showed that QSc/Sl.cib-2AS and QSc/Sl.cib-2AL were possibly two novel loci for SC and SL. QSc/Sl.cib-2AS and QSc/Sl.cib-2D showed pleiotropic effects on plant height and grain morphology, while QSc/Sl.cib-2AL showed effects on spikelet number per spike (SNS) and grain width (GW). Based on the gene annotation, orthologous search, and spatiotemporal expression patterns of genes, TraesCS2A03G0410600 and TraesCS2A03G0422300 for QSc/Sl.cib-2AS, and TraesCS2D03G1129300 and TraesCS2D03G1131500 for QSc/Sl.cib-2D were considered as potential candidate genes, respectively. These results will be useful for fine mapping and developing new varieties with high yield in the future.
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Flag leaf size is a crucial trait influencing plant architecture and yield potential in wheat. A recombinant inbred line (RIL) population derived from the cross of W7268 and Chuanyu 12 was employed to identify quantitative trait loci (QTL) controlling flag leaf length (FLL), flag leaf width (FLW), and flag leaf area (FLA) in six environments and the best linear unbiased estimator (BLUE) datasets. Using a 55 K SNP-based genetic map, six major and stable QTL were detected with 6.33-53.12% of explained phenotypic variation. Except for QFlw.cib-4B.3, the other five major QTL were co-located within two intervals on chromosomes 2B and 2D, namely QFll/Fla.cib-2B and QFll/Flw/Fla.cib-2D, respectively. Their interactions and effects on the corresponding traits and yield-related traits were also assessed based on flanking markers. QFll/Fla.cib-2B showed pleiotropic effects on spikelet number per spike (SNS). QFlw.cib-4B.3 and QFll/Flw/Fla.cib-2D had effects on grain number per spike (GNS) and thousand-grain weight (TGW). Comparison analysis suggested that QFll/Fla.cib-2B was likely a new locus. Two candidate genes, TraesCS2B03G0222800 and TraesCS2B03G0230000, associated with leaf development within the interval of QFll/Fla.cib-2B were identified based on expression-pattern analysis, gene annotation, ortholog analysis, and sequence variation. The major QTL and markers reported here provide valuable information for understanding the genetic mechanism underlying flag leaf size as well as breeding utilization in wheat.
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Colored wheat is a valuable resource that is rich in anthocyanins and minerals and thus contributes additional nutritional value to a healthy human diet. However, the effects of nitrogen fertilization on anthocyanin content (AC) and the balance between quality and yield still merit discussion. In this study, blue, purple, and common-colored wheat genotypes were used to investigate three nutrient quality traits, seven processing quality traits, three yield traits and seven grain morphology traits at three nitrogen levels in two years to excavate their possible plasticity under low-nitrogen stress and the tradeoffs among these traits. The highest AC was found in the blue genotypes followed by the purple genotypes. Analysis of variance (ANOVA) showed that AC could be significantly increased by reducing N application, especially in the purple genotypes. Therefore, growing colored wheat with low nitrogen input could allow efficient harvesting of grain with higher AC. However, the other nutrient quality traits and most processing quality traits were observed to decrease under low-nitrogen (LN) stress. Additionally, a correlation analysis indicated that the nutrient quality traits had stable tradeoffs with thousand kernel weight at all N levels because of the significantly negative correlations among them. Therefore, the additive main effect and multiplicative interaction (AMMI) model was used to further identify the most suitable colored genotypes with the best yield potential and also nutrient quality relative characteristics under LN stress. The blue lines Lanmai2999 and purple varieties Zhongkezinuomai 168 were found to be specifically adapted to LN stress with the highest AC values and showed stable performance in the other nutrient quality- and yield-related features. To further investigate the possible mechanism of anthocyanin accumulation in response to reduced N application, the expression of four genes (TaCHS, TaFDR, TaCHI and TaANS) involved in the anthocyanin synthesis pathway was evaluated. All four genes were downregulated under high nitrogen fertilizer application, indicating that anthocyanin synthesis in colored wheat might be inhibited by nitrogen fertilizer. Therefore, this research provided information for optimizing nitrogen fertilizer management in producing colored wheat and also demonstrated that it is efficient and economical to plant colored wheat genotypes in nitrogen-poor areas for use in a healthy human diet, improving the benefits of wheat planting and facilitating nitrogen pollution control.
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Antocianinas/genética , Grano Comestible/genética , Nitrógeno/metabolismo , Triticum/genética , Grano Comestible/crecimiento & desarrollo , Fertilizantes , Regulación de la Expresión Génica de las Plantas/genética , Genotipo , Glútenes/metabolismo , Humanos , Nutrientes , Fenotipo , Fitomejoramiento , Proteínas de Plantas/genética , Triticum/crecimiento & desarrolloRESUMEN
OBJECTIVES: To evaluate the efficacy and safety of leflunomide (LEF) and glucocorticoids (GCs) combination therapy compared with GCs monotherapy in preventing relapse of IgG4-related disease (IgG4-RD). METHODS: A 12-month, randomized, open-label, controlled trial was conducted at a large academic medical center (ClinicalTrials.gov: NCT02703194). Enrolled patients with active IgG4-RD were randomly allocated to the GCs + LEF (20 mg/day) combination therapy or GCs monotherapy group. All patients received GCs with a predefined taper regimen starting from a dosage of 0.5-0.8 mg/kg/d. The primary outcome was the time to relapse. The secondary outcomes included complete response, remission, GCs dosage, and serum IgG4 level. RESULTS: Sixty-six patients with active IgG4-RD were enrolled (33 patients in each group). The demographic and disease characteristics showed no statistically significant differences between groups. Additionally, the initial GCs dosages were similar (50.00 vs. 50.00 mg/day, P = 0.295). Disease relapses occurred in 6 (18.2%) and 14 (42.4%) patients in the combination therapy group and GCs monotherapy group, respectively (P = 0.032). The combination therapy was significantly superior to GCs monotherapy regarding the primary outcome, the time to relapse (HR, 0.35; 95% confidence interval [CI], 0.13-0.90; P = 0.023), as well as the secondary outcome, the time to complete response (HR, 1.75; 95% CI, 1.01-3.02; P = 0.034). A longer duration of remission was observed in the combination therapy group (7.00 vs. 3.00 months, P = 0.002) and less cumulative dosage of GCs was used (5103.13 vs. 5637.50 mg, P = 0.031). Additionally, a higher proportion of patients in the combination therapy group (54.5%) were able to reach a daily GCs dose of ≤5 mg/day compared with the GCs monotherapy group (18.2%) (P = 0.006). The incidences of adverse events were similar in the 2 groups (P = 0.325). CONCLUSION: LEF in combination with GCs therapy is well-tolerated and significantly superior to GCs monotherapy in preventing the relapse of IgG4-RD. LEF can be used as a steroid-sparing agent in the management of IgG4-RD.