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Genetic diversity is key to crop improvement. Owing to pervasive genomic structural variation, a single reference genome assembly cannot capture the full complement of sequence diversity of a crop species (known as the 'pan-genome'1). Multiple high-quality sequence assemblies are an indispensable component of a pan-genome infrastructure. Barley (Hordeum vulgare L.) is an important cereal crop with a long history of cultivation that is adapted to a wide range of agro-climatic conditions2. Here we report the construction of chromosome-scale sequence assemblies for the genotypes of 20 varieties of barley-comprising landraces, cultivars and a wild barley-that were selected as representatives of global barley diversity. We catalogued genomic presence/absence variants and explored the use of structural variants for quantitative genetic analysis through whole-genome shotgun sequencing of 300 gene bank accessions. We discovered abundant large inversion polymorphisms and analysed in detail two inversions that are frequently found in current elite barley germplasm; one is probably the product of mutation breeding and the other is tightly linked to a locus that is involved in the expansion of geographical range. This first-generation barley pan-genome makes previously hidden genetic variation accessible to genetic studies and breeding.
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Cromossomos de Plantas/genética , Genoma de Planta/genética , Hordeum/genética , Internacionalidade , Mutação , Melhoramento Vegetal , Inversão Cromossômica/genética , Mapeamento Cromossômico , Loci Gênicos/genética , Genótipo , Hordeum/classificação , Polimorfismo Genético/genética , Padrões de Referência , Banco de Sementes , Inversão de Sequência , Sequenciamento Completo do GenomaRESUMO
Three unusual ajmaline-macroline type bisindole alkaloids, alsmaphylines A-C, together with their postulated biogenetic precursors, were isolated from the stem barks and leaves of Alstonia macrophylla via the building blocks-based molecular network (BBMN) strategy. Alsmaphyline A represents a rare ajmaline-macroline type bisindole alkaloid with an S-shape polycyclic ring system. Alsmaphylines B and C are two novel ajmaline-macroline type bisindole alkaloids with N-1-C-21' linkages, and the former possesses an unconventional stacked conformation due to the presence of intramolecular noncovalent interactions. The chemical structures including absolute configurations of alsmaphylines A-C were established by comprehensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray crystallography. In addition, a plausible biosynthetic pathway of these bisindole alkaloids as well as their ability to promote the protein synthesis on HT22 cells were discussed.
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Alcaloides , Alstonia , Oxindóis , Alstonia/química , Ajmalina , Alcaloides Indólicos/química , Estrutura Molecular , Alcaloides/químicaRESUMO
Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 µM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.
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INTRODUCTION: We analyzed the effect of dexmedetomidine (DEX) as a local anesthetic adjuvant on postoperative delirium (POD) in elderly patients undergoing elective hip surgery. METHODS: In this study, 120 patients undergoing hip surgery were enrolled and randomly assigned to two groups: fascia iliaca compartment block with DEX + ropivacaine (the Y group, n = 60) and fascia iliaca compartment block with ropivacaine (the R group, n = 60). The primary outcomes: presence of delirium during the postanesthesia care unit (PACU) period and on the first day (D1), the second day (D2), and the third day (D3) after surgery. The secondary outcomes: preoperative and postoperative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), occurrence of insomnia on the preoperative day, day of operation, D1 and D2; HR values of patients in both groups before iliac fascia block (T1), 30 min after iliac fascia block (T2), at surgical incision (T3), 20 min after incision (T4), when they were transferred out of the operating room (T5) and after leaving the recovery room (T6) at each time point; VAS for T1, PACU, D1, D2; the number of patients requiring remedial analgesics within 24 h after blockade and related complications between the two groups. RESULTS: A total of 97 patients were included in the final analysis, with 11 and 12 patients withdrawing from the R and Y groups, respectively. The overall incidence of POD and its incidence in the PACU and ward were all lesser in the Y group than in the R group (p < 0.05). Additionally, fewer cases required remedial analgesia during the PACU period, and more vasoactive drugs were used for maintaining circulatory system stability in the Y group as compared to the R group (p < 0.05). At the same time, the incidence of intraoperative and postoperative bradycardia in the Y group was higher than that in the R group, accompanied by lower postoperative CRP and ESR (all p < 0.05). CONCLUSION: Ultrasound-guided high fascia iliaca compartment block with a combination of ropivacaine and DEX can reduce the incidence of POD, the use of intraoperative opioids and postoperative remedial analgesics, and postoperative inflammation in elderly patients who have undergone hip surgery, indicating that this method could be beneficial in the prevention and treatment of POD.
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Anestésicos Locais , Dexmedetomidina , Procedimentos Cirúrgicos Eletivos , Bloqueio Nervoso , Ropivacaina , Humanos , Dexmedetomidina/administração & dosagem , Masculino , Idoso , Feminino , Anestésicos Locais/administração & dosagem , Bloqueio Nervoso/métodos , Ropivacaina/administração & dosagem , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/métodos , Fáscia , Idoso de 80 Anos ou mais , Delírio do Despertar/prevenção & controle , Delírio do Despertar/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Quadril/cirurgia , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodosRESUMO
Four new alkaloids, arecatines A-D (1-4), were isolated from the peels of Areca catechu. Compound 1 is an unusual piperidine-pyridine hybrid alkaloid, whereas compounds 2-4 feature bis-piperidine alkaloids. Their structures were elucidated by UV, IR, HRESIMS, and NMR spectra analysis. The molecular docking analysis indicated that compound 3 exhibited the best binding affinity with the GABAA receptor, indicating its potential anti-epilepsy activity.
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Divergent selection of populations in contrasting environments leads to functional genomic divergence. However, the genomic architecture underlying heterogeneous genomic differentiation remains poorly understood. Here, we de novo assembled two high-quality wild barley (Hordeum spontaneum K. Koch) genomes and examined genomic differentiation and gene expression patterns under abiotic stress in two populations. These two populations had a shared ancestry and originated in close geographic proximity but experienced different selective pressures due to their contrasting micro-environments. We identified structural variants that may have played significant roles in affecting genes potentially associated with well-differentiated phenotypes such as flowering time and drought response between two wild barley genomes. Among them, a 29-bp insertion into the promoter region formed a cis-regulatory element in the HvWRKY45 gene, which may contribute to enhanced tolerance to drought. A single SNP mutation in the promoter region may influence HvCO5 expression and be putatively linked to local flowering time adaptation. We also revealed significant genomic differentiation between the two populations with ongoing gene flow. Our results indicate that SNPs and small SVs link to genetic differentiation at the gene level through local adaptation and are maintained through divergent selection. In contrast, large chromosome inversions may have shaped the heterogeneous pattern of genomic differentiation along the chromosomes by suppressing chromosome recombination and gene flow. Our research offers novel insights into the genomic basis underlying local adaptation and provides valuable resources for the genetic improvement of cultivated barley.
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Hordeum , Hordeum/genética , Genômica , Adaptação Fisiológica/genética , Genes de PlantasRESUMO
Cereal grasses of the Triticeae tribe have been the major food source in temperate regions since the dawn of agriculture. Their large genomes are characterized by a high content of repetitive elements and large pericentromeric regions that are virtually devoid of meiotic recombination. Here we present a high-quality reference genome assembly for barley (Hordeum vulgare L.). We use chromosome conformation capture mapping to derive the linear order of sequences across the pericentromeric space and to investigate the spatial organization of chromatin in the nucleus at megabase resolution. The composition of genes and repetitive elements differs between distal and proximal regions. Gene family analyses reveal lineage-specific duplications of genes involved in the transport of nutrients to developing seeds and the mobilization of carbohydrates in grains. We demonstrate the importance of the barley reference sequence for breeding by inspecting the genomic partitioning of sequence variation in modern elite germplasm, highlighting regions vulnerable to genetic erosion.
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Cromossomos de Plantas/genética , Genoma de Planta/genética , Hordeum/genética , Núcleo Celular/genética , Centrômero/genética , Cromatina/genética , Cromatina/metabolismo , Mapeamento Cromossômico , Cromossomos Artificiais Bacterianos/genética , Variação Genética , Genômica , Haplótipos/genética , Meiose/genética , Sequências Repetitivas de Ácido Nucleico/genética , Sementes/genéticaRESUMO
OBJECTIVE: To evaluate the effect of the individualized positive end-expiratory pressure (PEEP) lung protection ventilation strategy by combining driving pressure (ΔP) and pulmonary ultrasound (LUS)-based titration on lung function and postoperative cognitive function in patients with chronic obstructive pulmonary disease (COPD) during laparoscopic surgery. METHODS: A total of 108 patients with COPD undergoing laparoscopic gastrointestinal surgery under general anesthesia were included in this study. They were randomly divided into three groups (n = 36): traditional volume ventilation group (Group C), fixed PEEP 5 cmH2O group (Group P), and ΔP combined with LUS-based PEEP titration in the resuscitation room group (Group T). All three groups were given volume ventilation mode, I:E = 1:2; In group C, VT was 10 mL/kg and PEEP was 0 cmH2O; In groups P and T, VT was 6 mL/kg and PEEP was 5 cmH2O; After mechanical ventilation for 15 min in Group T, ΔP in combination with LUS was used to titrate PEEP. The oxygenation index (PaO2/FiO2), airway platform pressure (Pplat), dynamic lung compliance (Cdyn), Montreal Cognitive Assessment (MoCA), and venous interleukin-6(IL-6) were recorded at the corresponding time points, and the final PEEP value in Group T was recorded. RESULTS: The final PEEP value of Group T was (6.4 ± 1.2) cmH2O; Compared with groups C and P: PaO2/FiO2 and Cdyn in Group T were significantly increased (P < 0.05) and value of IL-6 was significantly decreased (P < 0.05) at the corresponding time points. Compared with group C, the MoCA score on day 7 after surgery in Group T was significantly higher (P < 0.05). CONCLUSION: Compared with the traditional ventilation strategy, the individualized ΔP combined with LUS-based PEEP titration in patients with COPD during the perioperative period of laparoscopic surgery can play a better role in lung protection and can improve postoperative cognitive function.
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Interleucina-6 , Doença Pulmonar Obstrutiva Crônica , Humanos , Cognição , Ultrassonografia , Pulmão/diagnóstico por imagemRESUMO
Here, (-)-Tetrahydroalstonine (THA) was isolated from Alstonia scholaris and investigated for its neuroprotective effect towards oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced neuronal damage. In this study, primary cortical neurons were pre-treated with THA and then subjected to OGD/R induction. The cell viability was tested by the MTT assay, and the states of the autophagy-lysosomal pathway and Akt/mTOR pathway were monitored by Western blot analysis. The findings suggested that THA administration increased the cell viability of OGD/R-induced cortical neurons. Autophagic activity and lysosomal dysfunction were found at the early stage of OGD/R, which were significantly ameliorated by THA treatment. Meanwhile, the protective effect of THA was significantly reversed by the lysosome inhibitor. Additionally, THA significantly activated the Akt/mTOR pathway, which was suppressed after OGD/R induction. In summary, THA exhibited promising protective effects against OGD/R-induced neuronal injury by autophagy regulation through the Akt/mTOR pathway.
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Fármacos Neuroprotetores , Traumatismo por Reperfusão , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Oxigênio/metabolismo , Neurônios , Glucose/metabolismo , Traumatismo por Reperfusão/metabolismo , Fármacos Neuroprotetores/farmacologia , ApoptoseRESUMO
To study the chemical constituents from the stems and leaves of Humulus scandens, this study isolated thirteen compounds by different chromatographic methods including silica gel column, ODS, Sephadex LH-20 and preparative HPLC. Based on comprehensive analysis, the chemical structures were elucidated and identified as citrunohin A(1), chrysosplenetin(2), casticin(3), neoechinulin A(4), ethyl 1H-indole-3-carboxylate(5), 3-hydroxyacetyl-indole(6),(1H-indol-3-yl) oxoacetamide(7), inonotusic acid(8), arteannuin B(9), xanthotoxol(10), α-tocopherol quinone(11), eicosanyl-trans-p-coumarate(12), and 9-oxo-(10E,12E)-octadecadienoic acid(13). Among them, compound 1 was a new dihydrochalcone, and the other compounds were obtained from H. scandens for the first time.
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Chalconas , Medicamentos de Ervas Chinesas , Humulus , Indóis , Medicamentos de Ervas Chinesas/químicaRESUMO
The future of plant cultivar improvement lies in the evaluation of genetic resources from currently available germplasm. Today's gene pool of crop genetic diversity has been shaped during domestication and more recently by breeding. Recent efforts in plant breeding have been aimed at developing new and improved varieties from poorly adapted crops to suit local environments. However, the impact of these breeding efforts is poorly understood. Here, we assess the contributions of both historical and recent breeding efforts to local adaptation and crop improvement in a global barley panel by analysing the distribution of genetic variants with respect to geographic region or historical breeding category. By tracing the impact that breeding had on the genetic diversity of Hordeum vulgare (barley) released in Australia, where the history of barley production is relatively young, we identify 69 candidate regions within 922 genes that were under selection pressure. We also show that modern Australian barley varieties exhibit 12% higher genetic diversity than historical cultivars. Finally, field-trialling and phenotyping for agriculturally relevant traits across a diverse range of Australian environments suggests that genomic regions under strong breeding selection and their candidate genes are closely associated with key agronomic traits. In conclusion, our combined data set and germplasm collection provide a rich source of genetic diversity that can be applied to understanding and improving environmental adaptation and enhanced yields.
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Genoma de Planta/genética , Hordeum/genética , Melhoramento Vegetal , Austrália , Produção Agrícola , Domesticação , Genes de Plantas/genética , Variação GenéticaRESUMO
KEY MESSAGE: Key genes controlling flowering and interactions of different photoperiod alleles with various environments were identified in a barley MAGIC population. A new candidate gene for vernalisation requirements was also detected. Optimal flowering time has a major impact on grain yield in crop species, including the globally important temperate cereal crop barley (Hordeum vulgare L.). Understanding the genetics of flowering is a key avenue to enhancing yield potential. Although bi-parental populations were used intensively to map genes controlling flowering, their lack of genetic diversity requires additional work to obtain desired gene combinations in the selected lines, especially when the two parental cultivars did not carry the genes. Multi-parent mapping populations, which use a combination of four or eight parental cultivars, have higher genetic and phenotypic diversity and can provide novel genetic combinations that cannot be achieved using bi-parental populations. This study uses a Multi-parent advanced generation intercross (MAGIC) population from four commercial barley cultivars to identify genes controlling flowering time in different environmental conditions. Genome-wide association studies (GWAS) were performed using 5,112 high-quality markers from Diversity Arrays Technology sequencing (DArT-seq), and Kompetitive allele-specific polymerase chain reaction (KASP) genetic markers were developed. Phenotypic data were collected from fifteen different field trials for three consecutive years. Planting was conducted at various sowing times, and plants were grown with/without additional vernalisation and extended photoperiod treatments. This study detected fourteen stable regions associated with flowering time across multiple environments. GWAS combined with pangenome data highlighted the role of CEN gene in flowering and enabled the prediction of different CEN alleles from parental lines. As the founder lines of the multi-parental population are elite germplasm, the favourable alleles identified in this study are directly relevant to breeding, increasing the efficiency of subsequent breeding strategies and offering better grain yield and adaptation to growing conditions.
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Estudo de Associação Genômica Ampla , Hordeum , Alelos , Grão Comestível/genética , Marcadores Genéticos , Hordeum/genética , Fenótipo , Fotoperíodo , Melhoramento Vegetal , Locos de Características QuantitativasRESUMO
Eleven new pyranochromones, calomembranone A-K (1-11), two new pyranocoumarins, calopolyanolide E and F (12 and 13), together with six known analogues (14-19) were isolated from the leaves of Calophyllum membranaceum. Their structures and absolute configurations were elucidated by analysis of spectroscopic data, computational calculations, as well as X-ray crystallography of 4 and 9. The anti-inflammatory activities of all the isolates were evaluated by measuring their NO inhibitory effects in LPS-stimulated RAW 264.7 cells. Structure-activity relationships are also discussed. Compound 7 showed the strongest NO inhibition (IC50 = 0.92 µM). Oral administration of 7 dose-dependently reduced the paw swelling and downregulated neutrophil-to-lymphocyte ratio in the carrageenan-induced acute arthritis mice model. Molecular dynamics simulation and cellular thermal shift assay results indicated that 7 participated in a robust and stable interaction with the active site of TLR4. Compound 7 also suppressed the inflammation in arthritis through the regulation of TLR4 mediated signal transduction via IKK/NF-κB signaling pathway and the consequent reduction of IL-2, IL-4, and IL-5.
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Artrite , Calophyllum , Animais , Anti-Inflamatórios , Artrite/induzido quimicamente , Artrite/tratamento farmacológico , Calophyllum/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B , Células RAW 264.7 , Receptor 4 Toll-LikeRESUMO
OBJECTIVE: To evaluate the effects of doxofylline on inflammatory responses and oxidative stress during mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD). METHODS: Eight-week-old male Sprague Dawley rats were selected, and the COPD rat model was constructed. The rats were randomly divided into a model group (group M), a model + normal saline group (group N), a doxofylline group (group D), and a control group fed with conventional chow and given normal oxygen supply (group C) (n = 12 in each group). Tracheal intubation and mechanical ventilation were conducted in the rats in each group after anesthesia. A real-time intravenous infusion with 50 mg/kg of doxofylline was conducted in group D, and there was no drug intervention in groups C, N and M. Pathological manifestations of the pulmonary tissues were observed and compared among the groups. And some indicators were evaluated. RESULTS: (1) The pulmonary tissues of the rats in groups M, N, and D exhibited typical pathological histological changes of COPD. (2) Groups M, N, and D showed increased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue and BALF, and decreased PaO2 and IL-10 and SOD levels, compared with group C. (3). Group D showed decreased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue, and increased PaO2 and IL-10 and SOD levels, compared with group N or M. CONCLUSION: Doxofylline was shown to improve ventilation and air exchange during mechanical ventilation in rats with COPD, reduce the inflammatory response and oxidative stress, and mitigate the degree of pulmonary tissue injury.
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Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Teofilina/análogos & derivados , Animais , Modelos Animais de Doenças , Inflamação/metabolismo , Interleucina-10/metabolismo , Masculino , Doença Pulmonar Obstrutiva Crônica/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Respiração Artificial/métodos , Teofilina/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Two new xanthones, calmemxanthone A (1) and calmemxanthone B (2), along with eleven known compounds were isolated from the dried twigs of Calophyllum membranaceum Gardn. et Champ. The structures of compounds 1 and 2 were established by analysis of spectra and mass spectrometry data. The absolute configuration of compound 1 was confirmed by electronic circular dichroism (ECD) spectral analysis. The anti-inflammation action of these compounds were evaluated on lipopolysaccharide (LPS)-induced inflammatory damage to human endometrial stromal cells (HESCs), and the structure-activities of 1-13 were also discussed. Compound 10 presented the anti-inflammation action with an IC50 value of 20.3â µM, that might be relevant to the regulation of NF-κB signaling pathway via the suppression of TRIF, IKKα, and IκBα.
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Calophyllum , Células-Tronco Embrionárias Humanas , Xantonas , Anti-Inflamatórios/farmacologia , Calophyllum/química , Humanos , Estrutura Molecular , Xantonas/química , Xantonas/farmacologiaRESUMO
PURPOSE: Reconstruction of severe acetabular deficiency is extremely challenging in total hip arthroplasty (THA) revisions. Novel bispherical augments were designed to fill acetabular bone loss and facilitate restoration of hip center of rotation (HCOR). Current study aims to compare the outcomes of bispherical augments and tantalum augments. METHODS: Between July 2017 and December 2018, bispherical augments (BA group) were implanted in 25 patients (25 hips) and 22 patients (22 hips) underwent porous tantalum augments (TA group) reconstruction in revision THA. Clinical and radiographic results were evaluated for 25 hips in BA group and 20 hips in TA group at the final follow-up. The mean duration of follow-up was 2.9 years (range, 2.2 ~ 3.7) in BA group and 2.9 years (range, 2.3 ~ 3.8) in TA group. RESULTS: Harris hip scores, HCOR, and leg length discrepancy (LLD) correction did not differ between the treatment groups. The bispherical augments were located more closer to the medial-superior part (zone II) of acetabular shell while the majority of tantalum augments were located at the lateral-superior part (zone I) (P = 0.010). More screws were used in the BA group for augment fixation (mean 2.1 vs. 1.3) (P = 0.000). There was no evidence of loosening or migration in all hips. Only one dislocation occurred in BA group and treated with closed reduction, no recurrence of instability up to the final follow-up. CONCLUSION: The clinical and radiological outcomes of bispherical augments were comparable with tantalum augments; this technique was a reliable alternative method in severe acetabular deficiency reconstruction.
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Artroplastia de Quadril , Prótese de Quadril , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Seguimentos , Prótese de Quadril/efeitos adversos , Humanos , Falha de Prótese , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Nitrogen is a major determinant of grain yield and quality. As excessive use of nitrogen fertilizer leads to environmental pollution and high production costs, improving nitrogen use efficiency (NUE) is fundamental for a sustainable agriculture. Here, we dissected the role of the barley abnormal cytokinin response1 repressor 1 (HvARE1) gene, a candidate for involvement in NUE previously identified in a genome-wide association study, through natural variation analysis and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing. HvARE1 was predominantly expressed in leaves and shoots, with very low expression in roots under low nitrogen conditions. Agrobacterium-mediated genetic transformation of immature embryos (cv. Golden Promise) with single guide RNAs targeting HvARE1 generated 22 T0 plants, from which four T1 lines harbored missense and/or frameshift mutations based on genotyping. Mutant are1 lines exhibited an increase in plant height, tiller number, grain protein content, and yield. Moreover, we observed a 1.5- to 2.8-fold increase in total chlorophyll content in the flag leaf at the grain filling stage. Delayed senescence by 10-14 d was also observed in mutant lines. Barley are1 mutants had high nitrogen content in shoots under low nitrogen conditions. These findings demonstrate the potential of ARE1 in NUE improvement in barley.
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Edição de Genes , Hordeum , Sistemas CRISPR-Cas/genética , Estudo de Associação Genômica Ampla , Hordeum/genética , Nitrogênio/metabolismoRESUMO
KEY MESSAGE: Using genomic structural equation modelling, this research demonstrates an efficient way to identify genetically correlating traits and provides an effective proxy for multi-trait selection to consider the joint genetic architecture of multiple interacting traits in crop breeding. Breeding crop cultivars with optimal value across multiple traits has been a challenge, as traits may negatively correlate due to pleiotropy or genetic linkage. For example, grain yield and grain protein content correlate negatively with each other in cereal crops. Future crop breeding needs to be based on practical yet accurate evaluation and effective selection of beneficial trait to retain genes with the best agronomic score for multiple traits. Here, we test the framework of whole-system-based approach using structural equation modelling (SEM) to investigate how one trait affects others to guide the optimal selection of a combination of agronomically important traits. Using ten traits and genome-wide SNP profiles from a worldwide barley panel and SEM analysis, we revealed a network of interacting traits, in which tiller number contributes positively to both grain yield and protein content; we further identified common genetic factors affecting multiple traits in the network of interaction. Our method demonstrates an efficient way to identify genetically correlating traits and underlying pleiotropic genetic factors and provides an effective proxy for multi-trait selection within a whole-system framework that considers the joint genetic architecture of multiple interacting traits in crop breeding. Our findings suggest the promise of a whole-system approach to overcome challenges such as the negative correlation of grain yield and protein content to facilitating quantitative and objective breeding decisions in future crop breeding.
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Cromossomos de Plantas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/genética , Genoma de Planta , Melhoramento Vegetal/métodos , Locos de Características Quantitativas , Seleção Genética , Mapeamento Cromossômico/métodos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Nitrogen (N) is one of the most important macronutrients for crop growth and development. Large amounts of N fertilizers are applied exogenously to improve grain yield and quality, which has led to environmental pollution and high cost of production. Therefore, improvement of N use efficiency (NUE) is a very important aspect for sustainable agriculture. Here, a pilot experiment was firstly conducted with a set of barley genotypes with confirmed NUE to validate the fast NUE screening, using chlorate as an analogue to nitrate. High NUE genotypes were susceptible to chlorate-induced toxicity whereas the low NUE genotypes were tolerant. A total of 180 barley RILs derived from four parents (Compass, GrangeR, Lockyer and La Trobe) were further screened for NUE. Leaf chlorosis induced by chlorate toxicity was the key parameter observed which was later related to low-N tolerance of the RILs. There was a distinct variation in chlorate susceptibility of the RILs with leaf chlorosis in the oldest leaf ranging from 10 to 80%. A genome-wide association study (GWAS) identified 9 significant marker-trait associations (MTAs) conferring high chlorate sensitivity on chromosomes 2H (2), 3H (1), 4H (4), 5H (1) and Un (1). Genes flanking with these markers were retrieved as potential targets for genetic improvement of NUE. Genes encoding Ferredoxin 3, leucine-rich receptor-like protein kinase family protein and receptor kinase are responsive to N stress. MTA4H5468 which exhibits concordance with high NUE phenotype can further be explored under different genetic backgrounds and successfully applied in marker-assisted selection. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01239-8.
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Toads produce potent toxins, named bufadienolides, to defend against their predators. Pharmacological research has revealed that bufadienolides are potential anticancer drugs. In this research, we reported nine bufadienolides from the eggs of the toad Bufo bufo gargarizans, including two new compounds (1 and 3). The chemical structures of 1 and 3, as well as of one previously reported semisynthesized compound (2), were elucidated on the basis of extensive spectroscopic data interpretation, chemical methods, and X-ray diffraction analysis. Compound 1 is an unusual 19-norbufadienolide with rearranged A/B rings. A biological test revealed that compounds 2 and 4-8 showed potent cytotoxic activities toward human melanoma cell line SK-MEL-1 with IC50 values less than 1.0 µM. A preliminary mechanism investigation revealed that the most potent compound, 8, could induce apoptosis via PARP cleavage, while 5 and 6 significantly suppressed angiogenesis in zebrafish. Furthermore, an in vivo biological study showed that 5, 6, and 8 inhibit SK-MEL-1 cell growth significantly.