RESUMO
Fusarium head blight (FHB) of barley (Hordeum vulgare) causes yield losses and accumulation of trichothecene mycotoxins (e.g. deoxynivalenol [DON]) in grains. Glucosylation of DON to the nontoxic DON-3-O-glucoside (D3G) is catalyzed by UDP-glucosyltransferases (UGTs), such as barley UGT13248. We explored the natural diversity of UGT13248 in 496 barley accessions and showed that all carried potential functional alleles of UGT13248, as no genotypes showed strongly increased seedling sensitivity to DON. From a TILLING population, we identified 2 mutant alleles (T368I and H369Y) that, based on protein modeling, likely affect the UDP-glucose binding of UGT13248. In DON feeding experiments, DON-to-D3G conversion was strongly reduced in spikes of these mutants compared to controls, and plants overexpressing UGT13248 showed increased resistance to DON and increased DON-to-D3G conversion. Moreover, field-grown plants carrying the T368I or H369Y mutations inoculated with Fusarium graminearum showed increased FHB disease severity and reduced D3G production. Barley is generally considered to have type II resistance that limits the spread of F. graminearum from the infected spikelet to adjacent spikelets. Point inoculation experiments with F. graminearum showed increased infection spread in T368I and H369Y across the spike compared to wild type, while overexpression plants showed decreased spread of FHB symptoms. Confocal microscopy revealed that F. graminearum spread to distant rachis nodes in T368I and H369Y mutants but was arrested at the rachis node of the inoculated spikelet in wild-type plants. Taken together, our data reveal that UGT13248 confers type II resistance to FHB in barley via conjugation of DON to D3G.
Assuntos
Fusarium , Hordeum , Hordeum/genética , Hordeum/metabolismo , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Difosfato de Uridina/metabolismo , Doenças das Plantas/genéticaRESUMO
In this paper, six silyl [PSiP] pincer cobalt(II) chlorides 1-6 [(2-Ph2PC6H4)2MeSiCo(Cl)(PMe3)] (1), [(2-Ph2PC6H4)2HSiCo(Cl)(PMe3)] (2), [(2-Ph2PC6H4)2PhSiCo(Cl)(PMe3)] (3), [(2-iPr2PC6H4)2HSiCo(Cl)(PMe3)] (4), [(2-iPr2PC6H4)2MeSiCo(Cl)(PMe3)] (5), and [(2-iPr2PC6H4)2PhSiCo(Cl)(PMe3)] (6)) were prepared from the corresponding [PSiP] pincer preligands (L1-L6), CoCl2 and PMe3 by Si-H bond activation. The catalytic activity of complexes 1-6 for alkene hyrdosilylation was studied. It was confirmed that complex 1 is the best catalyst with excellent regioselectivity among the six complexes. Using 1 as the catalyst, the catalytic reaction was completed within 1 h at 50 °C, predominantly affording Markovnikov products for aryl alkenes and anti-Markovnikov products for aliphatic alkene substrates. During the investigation of the catalytic mechanism, the Co(II) hydrides [(2-Ph2PC6H4)2MeSiCo(H)(PMe3)] (8) and [(2-iPr2PC6H4)2MeSiCo(H)(PMe3)] (9) were obtained from the stoichiometric reactions of complex 1 and 5 with NaBHEt3, respectively. Complexes 8 and 9 could also be obtained by the reactions of preligands L1 and L5 with Co(PMe3)4 via Si-H bond cleavage. More experiments corroborated that complex 8 is the real catalyst for this catalytic system. Under the same catalytic conditions as complex 1, using complex 8 as a catalyst, complete conversion of styrene was also achieved in 1 h, and the selectivity remained unchanged. Based on the experimental results, we propose a plausible mechanism for this catalytic reaction. The addition of B(C6F5)3 to catalyst 1 can reverse the selectivity of styrene hydrosilylation from the Markovnikov product as the main product (b/l = 99:1) to the anti-Markovnikov product as the main product (b/l = 40:60). Further study indicated that using the (CoCl2 + L1) system instead of complex 1, the selectivity was changed from Markovnikov to anti-Markovnikov product (b/l = 1:99.7). Therefore, the selectivity for the substrate styrene is influenced by the presence of a PMe3 ligand. The different selectivities may be caused by different active species. For the system of complex 1, a cobalt(II) hydride is the real catalyst, but for the (CoCl2 + L1) system, a cobalt(I) complex is proposed as active species. The molecular structures of Co(II) compounds 5 and 9 were resolved by single-crystal X-ray diffraction.
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Little is known about the selection pressures acting on plant pathogen populations, especially those applied by quantitative forms of resistance. Fusarium graminearum causes Fusarium head blight in wheat, producing significant yield losses and mycotoxin contamination. Quantitative host resistance is the best method to control Fusarium head blight. However, there needs to be more understanding of how disease resistance affects the evolution of plant pathogens. The aim of this study was to determine if the presence or absence of wheat resistance influenced the fitness components and genomic regions of F. graminearum. Thirty-one isolates from highly susceptible and 25 isolates from moderately resistant wheat lines were used. Isolate aggressiveness was measured by the area under the disease progress curve, visually damaged kernels, and deoxynivalenol contamination. The in vitro growth rate and spore production were also measured. Two whole-genome scans for selection were conducted with 333,297 single-nucleotide polymorphisms. One scan looked for signatures of selection in the entire sample, and the other scan was for divergent selection between the isolates from moderately resistant wheat and highly susceptible wheat. The subsample of isolates from highly susceptible wheat was primarily aggressive. Several regions of the F. graminearum genome with signatures for selection were identified. The moderately resistant wheat varieties used in this study did not select more aggressive isolates, suggesting that quantitative resistance is a durable method to control Fusarium head blight.
Assuntos
Resistência à Doença , Fusarium , Doenças das Plantas , Triticum , Fusarium/fisiologia , Fusarium/genética , Fusarium/patogenicidade , Triticum/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Resistência à Doença/genética , Tricotecenos/metabolismo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Fusarium head blight (FHB), mainly incited by Fusarium graminearum, has caused great losses in grain yield and quality of wheat globally. Fhb7, a major gene from 7E chromosome of Thinopyrum ponticum, confers broad resistance to multiple Fusarium species in wheat and has recently been cloned and identified as encoding a glutathione S-transferase (GST). However, some recent reports raised doubt about whether GST is the causal gene of Fhb7. To resolve the discrepancy and validate the gene function of GST in wheat, we phenotyped Fhb7 near-isogenic lines (Jimai22-Fhb7 versus Jimai22) and GST overexpressed lines for FHB resistance. Jimai22-Fhb7 showed significantly higher FHB resistance with a lower percentage of symptomatic spikelets, Fusarium-damaged kernels, and deoxynivalenol content than susceptible Jimai22 in three experiments. All the positive GST transgenic lines driven by either the maize ubiquitin promoter or its native promoter with high gene expression in the wheat cultivar 'Fielder' showed high FHB resistance. Only one maize ubiquitin promoter-driven transgenic line showed low GST expression and similar susceptibility to Fielder, suggesting that high GST expression confers Fhb7 resistance to FHB. Knockout of GST in the Jimai22-Fhb7 line using CRISPR-Cas9-based gene editing showed significantly higher FHB susceptibility compared with the nonedited control plants. Therefore, we confirmed GST as the causal gene of Fhb7 for FHB resistance. Considering its major effect on FHB resistance, pyramiding Fhb7 with other quantitative trait loci has a great potential to create highly FHB-resistant wheat cultivars.
Assuntos
Resistência à Doença , Fusarium , Glutationa Transferase , Doenças das Plantas , Triticum , Fusarium/fisiologia , Triticum/microbiologia , Triticum/genética , Triticum/enzimologia , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Resistência à Doença/genética , Plantas Geneticamente Modificadas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Poaceae/microbiologia , Poaceae/genéticaRESUMO
AIM: With the advancement of anti-cancer medicine, cardiovascular toxicities due to cancer therapies are common in oncology patients, resulting in increased mortality and economic burden. Cardiovascular toxicities caused by cancer therapies include different severities of cardiomyopathy, arrhythmia, myocardial ischaemia, hypertension, and thrombosis, which may lead to left ventricular dysfunction and heart failure. This scoping review aimed to summarise the mechanisms of cardiovascular toxicities following various anti-cancer treatments and potential predictive biomarkers for early detection. METHODS: PubMed, Cochrane, Embase, Web of Science, Scopus, and CINAHL databases were searched for original studies written in English related to the mechanisms of cardiovascular toxicity induced by anti-cancer therapies, including chemotherapy, targeted therapy, immunotherapy, radiation therapy, and relevant biomarkers. The search and title/abstract screening were conducted independently by two reviewers, and the final analysed full texts achieved the consensus of the two reviewers. RESULTS: A total of 240 studies were identified based on their titles and abstracts. In total, 107 full-text articles were included in the analysis. Cardiomyocyte and endothelial cell apoptosis caused by oxidative stress injury, activation of cell apoptosis, blocking of normal cardiovascular protection signalling pathways, overactivation of immune cells, and myocardial remodelling were the main mechanisms. Promising biomarkers for anti-cancer therapies related to cardiovascular toxicity included placental growth factor, microRNAs, galectin-3, and myeloperoxidase for the early detection of cardiovascular toxicity. CONCLUSION: Understanding the mechanisms of cardiovascular toxicity following various anti-cancer treatments could provide implications for future personalised treatment methods to protect cardiovascular function. Furthermore, specific early sensitive and stable biomarkers of cardiovascular system damage need to be identified to predict reversible damage to the cardiovascular system and improve the effects of anti-cancer agents.
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Antineoplásicos , Biomarcadores , Doenças Cardiovasculares , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Biomarcadores/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/diagnóstico , Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Cardiotoxicidade/diagnósticoRESUMO
With the trend towards ageing population globally, the salutogenic model can be integrated in interventions for pre-ageing and older adults to better support healthy ageing. However, there is limited research examining the salutogenic model's pathway amongst pre-ageing and older adults. Hence, this study aims to investigate pathways of the salutogenic model amongst pre-ageing and older adults with chronic diseases. Two hundred and eight pre-ageing and older adults were recruited from 11 Senior Activity Centres in Singapore. Data was collected using a self-reported questionnaire and analysed using path analyses. The indirect pathway from Subjective Cognitive Complaints to self-care abilities via sense of coherence and health practices were significant. Participants with higher sense of coherence may have increased capacities to execute more complex forms of self-care. Future interventions integrating the salutogenic model could enhance pre-ageing and older adults' self-care abilities to cope with chronic diseases and contribute to healthy ageing.
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The plant pathogenic fungus Fusarium graminearum is the causal agent of Fusarium head blight (FHB) disease on small-grain cereals. F. graminearum produces trichothecene mycotoxins such as deoxynivalenol (DON) that are required for full virulence. DON must be exported outside the cell to cause FHB disease, a process that may require the involvement of membrane-bound transporters. In this study, we show that the deletion of membrane-bound transporters results in reduced DON accumulation as well as reduced FHB symptoms on wheat. Deletion of the ATP-binding cassette (ABC) transporter gene Abc1 results in the greatest reduction in DON accumulation and virulence. Deletion of another ABC transporter gene, Abc6, also reduces FHB symptoms to a lesser degree. Combining deletions fails to reduce DON accumulation or virulence in an additive fashion, even when a ∆abc1 deletion is included. Heterologous expression of F. graminearum transporters in a DON-sensitive strain of yeast confirms Abc1 as a major DON resistance mechanism; furthermore, it suggests that Abc1 is directly participating in DON transport rather than facilitating DON transport though other means. Yeast expression further indicates that multiple transporters, including Abc1, play an important role in resistance to the wheat phytoalexin 2-benzoxazolinone (BOA) and other xenobiotics. Thus, Abc1 may contribute to virulence on wheat both by facilitating export of DON and by providing resistance to the wheat phytoalexin BOA. This research provides useful information that may aid in designing novel management techniques of FHB or other destructive plant diseases.
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Fusarium , Tricotecenos , Triticum/microbiologia , Virulência , Saccharomyces cerevisiae , Fitoalexinas , Xenobióticos/metabolismo , Doenças das Plantas/microbiologia , Tricotecenos/metabolismoRESUMO
Fusarium head blight (FHB) is among the chief threats to profitable barley production, and fungicide applications are one of two main strategies for reducing FHB damage to barley crops. However, there is very little published information on optimal timing of such applications. A 4-year field study was conducted with winter barley in Raleigh, North Carolina, to compare three timings for fungicide application: 50% spike emergence (Zadoks growth stage or GS 55), 100% spike emergence (GS 59), and 6 days after GS 59. Three winter barley cultivars with varying levels of FHB resistance were grown for four successive years (2018 to 2021) in a split-plot experiment and inoculated each spring with Fusarium-infected corn spawn. Three fungicides were compared: propiconazole + pydiflumetofen (Miravis Ace), prothioconazole + tebuconazole (Prosaro), and metconazole (Caramba). Correlations among visual symptoms and assays of harvested grain were modest and were weakened by fungicide applications. Across years and cultivars, deoxynivalenol (DON) and percent Fusarium-infected kernels were most reduced relative to the nontreated control by fungicide applications at the latest timing (GS 59 + 6 days). The early (GS 55) timing resulted in DON not significantly different from the nontreated control. Based on these results, it is recommended that to minimize damage from FHB, fungicide should be applied to winter barley several days after GS 59 (100% spike emergence), and not before GS 59.
Assuntos
Fungicidas Industriais , Fusarium , Hordeum , Fungicidas Industriais/farmacologia , Doenças das Plantas/prevenção & controle , TriticumRESUMO
Approximately 17% of the land worldwide is considered highly vulnerable to non-native plant invasion, which can dramatically alter nutrient cycles and influence greenhouse gas (GHG) emissions in terrestrial and wetland ecosystems. However, a systematic investigation of the impact of non-native plant invasion on GHG dynamics at a global scale has not yet been conducted, making it impossible to predict the exact biological feedback of non-native plant invasion to global climate change. Here, we compiled 273 paired observational cases from 94 peer-reviewed articles to evaluate the effects of plant invasion on GHG emissions and to identify the associated key drivers. Non-native plant invasion significantly increased methane (CH4 ) emissions from 129 kg CH4 ha-1 year-1 in natural wetlands to 217 kg CH4 ha-1 year-1 in invaded wetlands. Plant invasion showed a significant tendency to increase CH4 uptakes from 2.95 to 3.64 kg CH4 ha-1 year-1 in terrestrial ecosystems. Invasive plant species also significantly increased nitrous oxide (N2 O) emissions in grasslands from an average of 0.76 kg N2 O ha-1 year-1 in native sites to 1.35 kg N2 O ha-1 year-1 but did not affect N2 O emissions in forests or wetlands. Soil organic carbon, mean annual air temperature (MAT), and nitrogenous deposition (N_DEP) were the key factors responsible for the changes in wetland CH4 emissions due to plant invasion. The responses of terrestrial CH4 uptake rates to plant invasion were mainly driven by MAT, soil NH4 + , and soil moisture. Soil NO3 - , mean annual precipitation, and N_DEP affected terrestrial N2 O emissions in response to plant invasion. Our meta-analysis not only sheds light on the stimulatory effects of plant invasion on GHG emissions from wetland and terrestrial ecosystems but also improves our current understanding of the mechanisms underlying the responses of GHG emissions to plant invasion.
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Gases de Efeito Estufa , Óxido Nitroso , Carbono , Dióxido de Carbono/análise , Mudança Climática , Ecossistema , Espécies Introduzidas , Metano/análise , Nitrogênio , Óxido Nitroso/análise , Solo , Áreas AlagadasRESUMO
Smoking is a risk factor for dementia. Cognitive function can be partially restored after quitting smoking, but still lower than never smoked group. The underlying mechanisms still remain unclear. The effects of smoking cessation combined with cerebral chronic hypoperfusion (CCH) on cognitive function have never been described. Here, we established a cigarette smoking cessation model, a CCH model, and a cigarette smoking cessation plus CCH model. We investigated cognitive function in these models and the mechanisms of the neuroinflammation, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)/cysteine aspartate-specific proteinase (caspase-1)/interleukin- 1ß (IL-1ß) pathway, and eucaryotic initiation factor 2α (eIF2α) /autophagy pathway. We used morris water maze (MWM) and novel object recognition (NOR) test to evaluate cognitive function in rats. Nissl staining was performed to observe cell morphology in the hippocampal CA1 area. A neuroinflammatory marker (glial fibrillary acidic protein, GFAP) was assessed by Western blot analysis and immunohistochemistry staining. IL-1ß levels were detected by ELISA. The protein levels of NLRP3/caspase-1/ IL-1ß and eIF2α/autophagy pathway were evaluated by Western blot analysis. LC3 was assessed by immunofluorescence staining. CCH can affect cognitive function by influencing neuroinflammation, NLRP3/caspase-1/IL-1ß pathway, and eIF2α/autophagy pathway. Past exposure to cigarette smoke can also affect cognitive function by influencing neuroinflammation and NLRP3/caspase-1/IL-1ß pathway, which may be induced by smoking and may not be alleviated after smoking cessation. Past exposure to cigarette smoke does not influence autophagy, which may be increased by smoking and then decrease to normal levels after smoking cessation. Past exposure to smoking can further aggravate cognitive impairment and neuroinflammation in VaD animals: cognitive impairment induced by CCH via neuroinflammation, NLRP3/caspase-1/IL-1ß, and eIF2α/autophagy pathway and cognitive impairment induced by past exposure to cigarette smoke via neuroinflammation and NLRP3/caspase-1/IL-1ß pathway. The combined group had the worst cognitive impairment because of harmful reasons.
Assuntos
Fumar Cigarros , Disfunção Cognitiva , Demência Vascular , Animais , Fumar Cigarros/efeitos adversos , Disfunção Cognitiva/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias , Ratos , FumarRESUMO
KEY MESSAGE: This study identified a significant number of QTL that are associated with FHB disease resistance in NMBU spring wheat panel by conducting genome-wide association study. Fusarium head blight (FHB) is a widely known devastating disease of wheat caused by Fusarium graminearum and other Fusarium species. FHB resistance is quantitative, highly complex and divided into several resistance types. Quantitative trait loci (QTL) that are effective against several of the resistance types give valuable contributions to resistance breeding. A spring wheat panel of 300 cultivars and breeding lines of Nordic and exotic origins was tested in artificially inoculated field trials and subjected to visual FHB assessment in the years 2013-2015, 2019 and 2020. Deoxynivalenol (DON) content was measured on harvested grain samples, and anther extrusion (AE) was assessed in separate trials. Principal component analysis based on 35 and 25 K SNP arrays revealed the existence of two subgroups, dividing the panel into European and exotic lines. We employed a genome-wide association study to detect QTL associated with FHB traits and identify marker-trait associations that consistently influenced FHB resistance. A total of thirteen QTL were identified showing consistent effects across FHB resistance traits and environments. Haplotype analysis revealed a highly significant QTL on 7A, Qfhb.nmbu.7A.2, which was further validated on an independent set of breeding lines. Breeder-friendly KASP markers were developed for this QTL that can be used in marker-assisted selection. The lines in the wheat panel harbored from zero to five resistance alleles, and allele stacking showed that resistance can be significantly increased by combining several of these resistance alleles. This information enhances breeders´ possibilities for genomic prediction and to breed cultivars with improved FHB resistance.
Assuntos
Resistência à Doença , Fusarium , Mapeamento Cromossômico , Resistência à Doença/genética , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Doenças das Plantas/genética , Triticum/genéticaRESUMO
The "Train Your Brain" (TYB) cognitive intervention group program was developed based on previous research with the goal of remediating cognitive impairments for elderly Singaporean people with mild cognitive impairment (MCI). This study reports a pilot evaluation of feasibility (defined as participant attendance, retention rate, satisfaction and usefulness) and preliminary efficacy of the TYB program. Nineteen participants with MCI aged ≥ 50 years were recruited from a memory clinic in Singapore, with 14 receiving the TYB intervention. Participants were allocated in order of recruitment into consecutive identical groups for a 9-session program on brain health and cognitive training. Participants received pre- and post-intervention measures of cognition and completed feedback forms reporting on satisfaction with, and utility of, the TYB program. TYB was well attended (85% attendance for the first 6 sessions; 83% for the full 9-session TYB program). Participant satisfaction was high, with positive participant feedback reporting that TYB offered useful cognitive strategies which participants could implement in their daily life. Despite the small sample size and absence of control group, repeated-measures t-tests revealed significant pre- to post-intervention intra-individual improvement in global cognition measured by the Montreal Cognitive Assessment, and in executive function on the Brixton Spatial Anticipation Test. This pilot study provides supportive preliminary evidence for feasibility of TYB, with suggestions of efficacy of this program as a culturally and linguistically appropriate intervention for English-speaking older adults with MCI in Singapore.
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Disfunção Cognitiva , Idoso , Encéfalo , Cognição , Disfunção Cognitiva/terapia , Estudos de Viabilidade , Humanos , Projetos Piloto , SingapuraRESUMO
Acute episodes of amnestic syndrome can be a challenging diagnostic problem. Except for nonvascular etiology, thalamic strokes or infarction involving several temporal lobe structures has been reported in earlier cases. The authors report a patient who suddenly developed memory loss without any other focal neurologic deficits. Brain magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) performed 1 day after onset revealed acute infarction involving the bilateral fornix column and the genu of corpus callosum. Because simple fornix infarcts often have no obvious positive neurological signs, most of the related manifestations were provided by family members, are easy to be diagnosed falsely, and missed in clinical areas, we suggest that bilateral fornix infarction should be considered in the diagnosis of an acute onset amnestic syndrome.
Assuntos
Amnésia , Fórnice , Amnésia/diagnóstico por imagem , Amnésia/etiologia , Amnésia/patologia , Fórnice/irrigação sanguínea , Fórnice/diagnóstico por imagem , Fórnice/patologia , Humanos , Infarto/complicações , Infarto/patologia , Imageamento por Ressonância Magnética , Transtornos da MemóriaRESUMO
OBJECTIVE: Minor stroke or transient ischemic attack (TIA) usually have mild and nondisabling symptoms, and these functional deficits may recover fully e.g., TIA, however, part of them still suffer from cognitive impairment and poor outcomes. We conducted a study to determine the relationship between cognition evaluated by Montreal Cognitive Assessment (MoCA) and poor functional outcomes assessed by the Modified Rankin Scale (mRS) (mRS ≥ 2) and Stroke Impact Scale (SIS)-16(SIS-16<25%). METHODS: The data of this study come from the impairment of cognition and Sleep (ICONS) after acute ischemic stroke or transient ischemic attack in Chinese patients study. A total of 1675 minor stroke patients and TIA patients were finally recruited. Patients' cognition were evaluated by Montreal Cognitive Assessment (MoCA) scale at 2-week (2w), 3 months (3 m) and 1 year(1y). Cognitive impairment (CI) was defined as MoCA score ≤ 22. According to MoCA score, patients were divided into 4 groups: no PSCI group: with MoCA-2w>22 and MoCA-3 m>22; improved PSCI group: with MoCA-2w ≤ 2 and MoCA-3 m>22;delayed PSCI group: MoCA-2w>22 and MoCA-3 m ≤ 22; persisting PSCI group: with MoCA-2w ≤ 22 and MoCA-3 m ≤ 22. RESULTS: A total of 1675 stroke patients were recruited in this study. There were 818 patients (48.84%) who had PSCI at baseline. Of these, 123 patients (15%) had mRS ≥2 at 3 months. The persisting PSCI group was a significant predictor of functional dependence at 3 months and 1 year after stroke and when adjusted for covariates such as gender, age, history of stroke, depression and intracranial atherosclerotic stenosis, stroke subtype and acute infarction type. CONCLUSION: Persisting PSCI increased the risk of poor functional outcome after 3 months and 1 year follow-up. These high-risk individuals should be identified for targeted rehabilitation and counseling to improve longer-term post-stroke outcome.
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Transtornos Cognitivos , Disfunção Cognitiva , Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/epidemiologia , Estudos de Coortes , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Estado Funcional , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapiaRESUMO
KEY MESSAGE: Discovery and mapping of a susceptibility factor located on the short arm of wheat chromosome 7A whose deletion makes plants resistant to Fusarium head blight. Fusarium head blight (FHB) disease of wheat caused by Fusarium spp. deteriorates both quantity and quality of the crop. Manipulation of susceptibility factors, the plant genes facilitating disease development, offers a novel and alternative strategy for enhancing FHB resistance in plants. In this study, a major effect susceptibility gene for FHB was identified on the short arm of chromosome 7A (7AS). Nullisomic-tetrasomic lines for homoeologous group-7 of wheat revealed dosage effect of the gene, with tetrasomic 7A being more susceptible than control Chinese Spring wheat, qualifying it as a genuine susceptibility factor. Five chromosome 7A inter-varietal substitution lines and a tetraploid Triticum dicoccoides 7A substitution line showed similar susceptibility as that of Chinese Spring, indicating toward the commonality of the susceptibility factor among these diverse genotypes. The susceptibility factor was named as Sf-Fhb-7AS and mapped on chromosome 7AS to a 48.5-50.5 Mb peri-centromeric region between del7AS-3 and del7AS-8. Our results showed that deletion of Sf-Fhb-7AS imparts 50-60% type 2 FHB resistance and its manipulation can be used to enhance resistance against FHB in wheat.
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Resistência à Doença/genética , Fusarium/patogenicidade , Doenças das Plantas/genética , Triticum/genética , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Dosagem de Genes , Genes de Plantas , Genótipo , Doenças das Plantas/microbiologiaRESUMO
KEY MESSAGE: Fine mapping of barley 6H pericentromeric region identified FHB QTL with opposite effects, and high grain protein content was associated with increased FHB severity. Resistance to Fusarium head blight (FHB), kernel discoloration (KD), deoxynivalenol (DON) accumulation and grain protein content (GPC) are important traits for breeding malting barley varieties. Previous work mapped a Chevron-derived FHB QTL to the pericentromeric region of 6H, coinciding with QTL for KD resistance and GPC. The Chevron allele reduced FHB and KD, but unfavorably increased GPC. To determine whether the correlations are caused by linkage or pleiotropy, a fine mapping approach was used to dissect the QTL underlying these quality and disease traits. Two populations, referred to as Gen10 and Gen10/Lacey, derived from a recombinant near-isogenic line (rNIL) were developed. Recombinants were phenotyped for FHB, KD, DON, GPC and other agronomic traits. Three FHB, two DON and two KD QTLs were identified. One of the three FHB QTLs, one DON QTL and one KD QTL were coincident with the GPC QTL, which contains the Hv-NAM1 locus affecting grain protein accumulation. The Chevron allele at the GPC QTL increased GPC and FHB and decreased DON and KD. The other two FHB QTL and the other DON and KD QTL were identified in the regions flanking the Hv-NAM1 locus, and the Chevron alleles decreased FHB, DON and KD. Our results suggested that the QTL associated with FHB, KD, DON and GPC in the pericentromeric region of 6H was controlled by both pleiotropy and tightly linked loci. The rNILs identified in this study with low FHB severity and moderate GPC may be used for breeding malting barley cultivars.
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Resistência à Doença/genética , Fusarium/patogenicidade , Proteínas de Grãos/análise , Hordeum/genética , Doenças das Plantas/genética , Alelos , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Pleiotropia Genética , Genótipo , Fenótipo , Doenças das Plantas/microbiologia , Locos de Características QuantitativasRESUMO
Selective introduction of the deuterium atom into the α-position of amines is important for the development of all types of novel deuterated drugs and agrochemicals due to the pervasive presence of amines. In this study, we report the first general single-electron-transfer reductive deuteration of both ketoximes and aldoximes using SmI2 as an electron donor and D2O as a deuterium source for the synthesis of α-deuterated primary amines with excellent levels of deuterium incorporations (>95% [D]). This protocol exhibits excellent chemoselectivity and tolerates a variety of functional groups. The potential application of this new method was showcased in the synthesis of deuterated drugs, such as rimantadine-d4, the tebufenpyrad analogue, derivatives of nabumetone and pregnenolone, and a series of building blocks for the rapid and general assembly of deuterated drugs and pesticides.
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Aminas , Oximas , DeutérioRESUMO
Six silyl cobalt(III) hydrides 1-6 with [PSiP] pincer ligands having different substituents at the P and Si atoms ([(2-Ph2PC6H4)2MeSiCo(H)(Cl)(PMe3)] (1), [(2-Ph2PC6H4)2HSiCo(H)(Cl)(PMe3)] (2), [(2-Ph2PC6H4)2PhSiCo(H)(Cl)(PMe3)] (3), [(2-iPr2PC6H4)2HSiCo(H)(Cl)(PMe3)] (4), [(2-iPr2PC6H4)2MeSiCo(H)(Cl)(PMe3)] (5), and [(2-iPr2PC6H4)2PhSiCo(H)(Cl)(PMe3)] (6)) were synthesized through the reactions of the ligands (L1-L6) with CoCl(PMe3)3 via Si-H bond cleavage. Compounds 1-6 have catalytic activity for alkene hydrosilylation, and among them, complex 3 is the best catalyst with excellent anti-Markovnikov regioselectivity. A silyl dihydrido cobalt(III) complex 7 from the reaction of 3 with Ph2SiH2 was isolated, and its catalytic activity is equivalent to that of complex 3. Complex 7 and its derivatives 10-12 could also be obtained through the reactions of complexes 3, 1, 4, and 5 with NaBHEt3. The molecular structure of 7 was indirectly verified by the structures of 10-12. To our delight, the addition of pyridine N-oxide reversed the selectivity of the reaction, from anti-Markovnikov to Markovnikov addition. At the same time, the reaction temperature was reduced from 70 to 30 °C on the premise of high yield and excellent selectivity. However, this catalytic system is only applicable to aromatic alkenes. On the basis of the experimental information, two reaction mechanisms are proposed. The molecular structures of cobalt(III) complexes 3-6 and 10-12 were determined by single crystal X-ray diffraction analysis.
RESUMO
Succinate dehydrogenase (SDH), a crucial bridge enzyme between the respiratory electron transfer chain and tricarboxylic acid (or Krebs) cycle, has been identified as an ideal target for the development of effective fungicide. In this study, a series of 24 novel SDH inhibitors (SDHIs) were designed, synthesized, and characterized by 1H NMR, 13C NMR, and HRMS. In vitro fungicidal activity experiments, most of the compounds exhibited broad-spectrum antifungal activities against five plant pathogenic fungi. Compounds 9j and 9k showed excellent activities against Pythium aphanidermatum with EC50 values of 9.93 mg/L and 10.50 mg/L, respectively, which were superior to the lead compound Fluopyram with an EC50 value of 19.10 mg/L. Furthermore, the toxicity of these compounds was also tested against Meloidogyne incognita J2 nematodes. The results indicated that compound 9x exhibited moderate nematicidal activity (LC50/48 h = 71.02 mg/L). Molecular docking showed that novel guanidine amide of 9j formed hydrogen bonds with crucial residues, which was crucial to the binding of an inhibitor and SDH. This present work indicates that these derivatives may serve as novel potential fungicides targeting SDH.
Assuntos
Antifúngicos/farmacologia , Benzamidas/farmacologia , Inibidores Enzimáticos/farmacologia , Fungos/efeitos dos fármacos , Guanidina/farmacologia , Piridinas/farmacologia , Succinato Desidrogenase/antagonistas & inibidores , Animais , Antifúngicos/síntese química , Antifúngicos/química , Benzamidas/síntese química , Benzamidas/química , Relação Dose-Resposta a Droga , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Guanidina/química , Testes de Sensibilidade Microbiana , Mitocôndrias Cardíacas/enzimologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Piridinas/síntese química , Piridinas/química , Relação Estrutura-Atividade , Succinato Desidrogenase/metabolismo , SuínosRESUMO
Understanding the metal pollution can help governments and estuary management groups manage metal inputs. Here, we comprehensively analyzed the behaviors of seven metals Cd, Zn, Cu, As, Pb, Cr, and Hg in water and the responses of these metals to hydrological connectivity in the Pearl River Estuary. The analyses were based on the field measurements of August-2016 in the estuary and January-2016 in the upper river mouth. We also assessed the ecosystem health of these metals. Overall, this estuary had an overall moderate pollution level, with occasional severe perturbations. The mean concentration of individual metal was in the order of Zn > As > Cu > Cr > Pb > Cd > Hg. The eastern estuary was more heavily polluted by metals (notably, Zn, Cd, and Cu) than the western estuary; this condition was attributable to sewage and industrial effluent discharges from the eastern urban cities of Dongguan and Shenzhen. Longitudinally, high levels of Cd and Zn appeared in the upper estuary, while elevated levels of Cu, As, Pb, Cr, and Hg were found in the middle and lower estuaries. The riverine inputs and estuarine mixing significantly influenced the distribution and movement of trace metals in the estuary, and have contributed to phytoplankton productivity (chlorophyll-a > 10 µg/L). River inflow inhibited the vertical diffusion of metals, and tidal currents facilitated surface-to-bottom mixing. Cu and Cd posed ecological risks. We determined the source contributions and transport routes of the metals using principal component analysis combining with multiple linear regression. The results of this study suggest that the source apportionment of metals can help to manage the source input entering into the estuary. Further, identified hydrological connectivity of metals can inform water quality managers in the highly anthropogenically influenced estuary.