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BACKGROUND: Bladder cancer (BLCA) is a prevalent malignancy worldwide. Anoikis remains a new form of cell death. It is necessary to explore Anoikis-related genes in the prognosis of BLCA. METHODS: We obtained RNA expression profiles from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases for dimensionality reduction analysis and isolated epithelial cells, T cells and fibroblasts for copy number variation analysis, pseudotime analysis and transcription factor analysis based on R package. We integrated machine-learning algorithms to develop the artificial intelligence-derived prognostic signature (AIDPS). RESULTS: The performance of AIDPS with clinical indicators was stable and robust in predicting BLCA and showed better performance in every validation dataset compared to other models. Mendelian randomization analysis was conducted. Single nucleotide polymorphism (SNP) sites of rs3100578 (HK2) and rs66467677 (HSP90B1) exhibited significant correlation of bladder problem (not cancer) and bladder cancer, whereasSNP sites of rs3100578 (HK2) and rs947939 (BAD) had correlation between bladder stone and bladder cancer. The immune infiltration analysis of the TCGA-BLCA cohort was calculated via the ESTIMATE (i.e. Estimation of STromal and Immune cells in MAlignantTumours using Expression data) algorithm which contains stromal, immune and estimate scores. We also found significant differences in the IC50 values of Bortezomib_1191, Docetaxel_1007, Staurosporine_1034 and Rapamycin_1084 among the high- and low-risk groups. CONCLUSIONS: In conclusion, these findings indicated Anoikis-related prognostic genes in BLCA and constructed an innovative machine-learning model of AIDPS with high prognostic value for BLCA.
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Anoicis , Neoplasias de la Vejiga Urinaria , Humanos , Anoicis/genética , Inteligencia Artificial , Variaciones en el Número de Copia de ADN , Neoplasias de la Vejiga Urinaria/genética , AlgoritmosRESUMEN
Driven by the strong adsorptive and catalytic ability of metal sulfides for soluble polysulfides, it is considered as a potential mediator to resolve the problems of shuttle effect and slow reaction kinetics of polysulfides in lithium-sulfur (Li-S) batteries. However, their further development is limited by poor electrical conductivity and bad long-term durability. Herein, one type of new catalyst composed of SnS/SnS2 heterostructures on hierarchical porous carbon (denoted as SnS/SnS2-HPC) by a simple hydrothermal method is reported and used as an interlayer coating on the conventional separator for blocking polysulfides. The SnS/SnS2-HPC integrates the advantages of a porous conductive network for promoting the transport of electrons and an enhanced electrocatalyst for accelerating polysulfides conversion. As a result, such a cell coupled with a SnS/SnS2-HPC interlayer exhibits a long-term lifespan of 1200 cycles. This work provides a new cell configuration by using heterostructures with a built-in electric field formed from a p-n heterojunction to improve the performance of Li-S batteries.
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Lithium-sulfur (Li-S) batteries with high specific energy density, low cost, and environmental friendliness of sulfur have been regarded as a competitive alternative to replace lithium-ion batteries. However, the shuttle effect and the sluggish conversion rate of lithium polysulfides (LiPSs) have seriously limited the practical application of Li-S batteries. Herein, high-entropy oxides grown on the carbon cloth (CC/HEO) are synthesized by a simple and ultrafast solution combustion method for the sulfur cathode. The as-prepared composites possess abundant HEO active sites for strong interaction with LiPSs, which can significantly promote redox kinetics. Besides, the carbon fiber substrate not only ensures high electrical conductivity but also accommodates large volume change, leading to a stable sulfur electrochemistry. Benefiting from the rational design, the Li-S batteries with CC/HEO as cathode skeleton exhibits good cyclability with a capacity decay rate of 0.057% per cycle after 1000 cycles at 2 C. More importantly, the Li-S batteries with 4.3 mg cm-2 high sulfur loading can still retain a high capacity retention of 78.2% after 100 cycles.
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Three-dimensional (3D) reduced graphene oxide (rGO)/Ti2CTx MXene hybrid aerogels were effectively prepared by a two-step method involving hydrothermal reaction and freeze-drying. The intimately coupled rGO/Ti2CTx hybrid aerogel combined high electrical conductivity, large interlayer spacing, and excellent mechanical stability of Ti2CTx, which not only effectively prevents the self-restacking of Ti2CTx nanosheets, exposes more active sites exposed, and improves the volume change during the charge/discharge process but also increases the accessibility of ions and promotes the rapid transfer of ions/electrons. As a result, rGO/Ti2CTx 17.5-2.5 as the working electrode of electric double layer capacitors delivers a large specific capacity (107.05 F g-1 at 0.5 A g-1 in a 1M Na2SO4 electrolyte), a high rate capability (maintains 30% of its initial capacitance at 10 A g-1, which is much better than rGO and Ti2CTx), and excellent long-term large-current cycle stability (the initial capacitance remains above 71.1% after 10 000 cycles at 1 A g-1). In addition to providing a high-performance electrode for supercapacitors, this study proposes an efficient and time-saving strategy for constructing 3D structures from 2D materials.
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KEY MESSAGE: We reported the graph-based mitochondrial genomes of three foundation species (Saccharum spontaneum, S. robustum and S. officinarum) for the first time. The results revealed pan-structural variation and evolutionary processes in the mitochondrial genomes within Saccharum. Saccharum belongs to the Andropogoneae, and cultivars species in Saccharum contribute nearly 80% of sugar production in the world. To explore the genomic studies in Saccharum, we assembled 15 complete mitochondrial genomes (mitogenome) of three foundation species (Saccharum spontaneum, S. robustum and S. officinarum) using Illumina and Oxford Nanopore Technologies sequencing data. The mitogenomes of the three species were divided into a total of eight types based on contig numbers and linkages. All mitogenomes in the three species encoded 51 unique genes, including 32 protein-coding, 3 ribosomal RNA (rRNA) and 16 transfer RNA (tRNA) genes. The existence of long and short-repeat-mediated recombinations in the mitogenome of S. officinarum and S. robustum was revealed and confirmed through PCR validation. Furthermore, employing comparative genomics and phylogenetic analyses of the organelle genomes, we unveiled the evolutionary relationships and history of the major interspecific lineages in Saccharum genus. Phylogenetic analyses of homologous fragments between S. officinarum and S. robustum showed that S. officinarum and S. robustum are phylogenetically distinct and that they were likely parallel rather than domesticated. The variations between ancient (S. sinense and S. barberi) and modern cultivated species (S. hybrid) possibly resulted from hybridization involving different S. officinarum accessions. Lastly, this project reported the first graph-based mitogenomes of three Saccharum species, and a systematic comparison of the structural organization, evolutionary processes, and pan-structural variation of the Saccharum mitogenomes revealed the differential features of the Saccharum mitogenomes.
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Genoma Mitocondrial , Filogenia , Saccharum , Genoma Mitocondrial/genética , Saccharum/genética , ARN de Transferencia/genética , Genoma de Planta/genética , ARN Ribosómico/genética , Evolución MolecularRESUMEN
Structural variations (SVs) are a feature of plant genomes that has been largely unexplored despite their significant impact on plant phenotypic traits and local adaptation to abiotic and biotic stress. In this study, we employed woolly grape (Vitis retordii), a species native to the tropical and subtropical regions of East Asia with both coastal and inland habitats, as a valuable model for examining the impact of SVs on local adaptation. We assembled a haplotype-resolved chromosomal reference genome for woolly grape, and conducted population genetic analyses based on whole-genome sequencing (WGS) data from coastal and inland populations. The demographic analyses revealed recent bottlenecks in all populations and asymmetric gene flow from the inland to the coastal population. In total, 1,035 genes associated with plant adaptive regulation for salt stress, radiation, and environmental adaptation were detected underlying local selection by SVs and SNPs in the coastal population, of which 37.29% and 65.26% were detected by SVs and SNPs, respectively. Candidate genes such as FSD2, RGA1, and AAP8 associated with salt tolerance were found to be highly differentiated and selected during the process of local adaptation to coastal habitats in SV regions. Our study highlights the importance of SVs in local adaptation; candidate genes related to salt stress and climatic adaptation to tropical and subtropical environments are important genomic resources for future breeding programs of grapevine and its rootstocks.
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Vitis , Vitis/genética , Adaptación Fisiológica/genética , Genoma de Planta/genética , Genética de Población , Polimorfismo de Nucleótido Simple/genética , Tolerancia a la Sal/genética , Variación Estructural del Genoma/genética , Genómica , Genes de PlantasRESUMEN
BACKGROUND: Sucrose phosphate synthase B (SPSB) gene encoding an important rate-limiting enzyme for sucrose synthesis in sugarcane is mainly expressed on leaves, where its alleles control sucrose synthesis. In this study, genetic variation of SPSB gene represented by different haplotypes in sugarcane was investigated in hybrid clones with high and low sugar content and various accessory species. RESULTS: A total of 39 haplotypes of SPSB gene with 2, 824 bp in size were identified from 18 sugarcane accessions. These haplotypes mainly distributed on Chr3B, Chr3C, and Chr3D according to the AP85-441 reference genome. Single nucleotide polymorphisms (SNPs) and insertion/deletion (InDels) were very dense (42 bp/sequence variation) including 44 transitional and 23 transversional SNPs among the 39 haplotypes. The sequence diversity related Hd, Eta, and Pi values were all lower in clones of high sucrose content (HS) than those in clones of low sucrose content (LS). The evolutionary network analysis showed that about half SPSB haplotypes (19 out of 39) were clustered into one group, including 6 (HAP4, HAP6, HAP7, HAP9, HAP17 and HAP20) haplotypes under positive selection in comparison to HAP26 identified in Badila (S. officinarum), an ancestry noble cane species and under purification selection (except HAP19 under neutral selection) in comparison to HAP18 identified from India1 (S. spontaneum), an ancestry species with low sugar content but high stress tolerance. The average number of haplotypes under positive selection in HS clones was twice as that in LS. Most of the SNPs and InDels sequence variation sites were positively correlated with sucrose and fiber content and negatively correlated with reducing sugar. CONCLUSIONS: A total of 39 haplotypes of SPSB gene were identified in this study. Haplotypes potentially associated with high sucrose synthesis efficiency were identified. The mutations of SPSB haplotypes in HS were favorable and tended to be selected and fixed. The results of this study are informative and beneficial to the molecular assisted breeding of sucrose synthesis in sugarcane in the future.
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Saccharum , Haplotipos , Saccharum/genética , Sacarosa , Glucosiltransferasas/genéticaRESUMEN
BACKGROUND: The studies on SARS-CoV-2 and human microbiota have yielded inconsistent results regarding microbiota α-diversity and key microbiota. To address these issues and explore the predictive ability of human microbiota for the prognosis of SARS-CoV-2 infection, we conducted a reanalysis of existing studies. METHODS: We reviewed the existing studies on SARS-CoV-2 and human microbiota in the Pubmed and Bioproject databases (from inception through October 29, 2021) and extracted the available raw 16S rRNA sequencing data of human microbiota. Firstly, we used meta-analysis and bioinformatics methods to reanalyze the raw data and evaluate the impact of SARS-CoV-2 on human microbial α-diversity. Secondly, machine learning (ML) was employed to assess the ability of microbiota to predict the prognosis of SARS-CoV-2 infection. Finally, we aimed to identify the key microbiota associated with SARS-CoV-2 infection. RESULTS: A total of 20 studies related to SARS-CoV-2 and human microbiota were included, involving gut (n = 9), respiratory (n = 11), oral (n = 3), and skin (n = 1) microbiota. Meta-analysis showed that in gut studies, when limiting factors were studies ruled out the effect of antibiotics, cross-sectional and case-control studies, Chinese studies, American studies, and Illumina MiSeq sequencing studies, SARS-CoV-2 infection was associated with down-regulation of microbiota α-diversity (P < 0.05). In respiratory studies, SARS-CoV-2 infection was associated with down-regulation of α-diversity when the limiting factor was V4 sequencing region (P < 0.05). Additionally, the α-diversity of skin microbiota was down-regulated at multiple time points following SARS-CoV-2 infection (P < 0.05). However, no significant difference in oral microbiota α-diversity was observed after SARS-CoV-2 infection. ML models based on baseline respiratory (oropharynx) microbiota profiles exhibited the ability to predict outcomes (survival and death, Random Forest, AUC = 0.847, Sensitivity = 0.833, Specificity = 0.750) after SARS-CoV-2 infection. The shared differential Prevotella and Streptococcus in the gut, respiratory tract, and oral cavity was associated with the severity and recovery of SARS-CoV-2 infection. CONCLUSIONS: SARS-CoV-2 infection was related to the down-regulation of α-diversity in the human gut and respiratory microbiota. The respiratory microbiota had the potential to predict the prognosis of individuals infected with SARS-CoV-2. Prevotella and Streptococcus might be key microbiota in SARS-CoV-2 infection.
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COVID-19 , Microbiota , Humanos , SARS-CoV-2 , Estudios Transversales , Disbiosis , ARN Ribosómico 16S , Pronóstico , PrevotellaRESUMEN
Nitrogen (N) is a vital mineral component that can restrict the growth and development of plants if supplied inappropriately. In order to benefit their growth and development, plants have complex physiological and structural responses to changes in their nitrogen supply. As higher plants have multiple organs with varying functions and nutritional requirements, they coordinate their responses at the whole-plant level based on local and long-distance signaling pathways. It has been suggested that phytohormones are signaling substances in such pathways. The nitrogen signaling pathway is closely associated with phytohormones such as auxin (AUX), abscisic acid (ABA), cytokinins (CKs), ethylene (ETH), brassinosteroid (BR), strigolactones (SLs), jasmonic acid (JA), and salicylic acid (SA). Recent research has shed light on how nitrogen and phytohormones interact to modulate physiology and morphology. This review provides a summary of the research on how phytohormone signaling affects root system architecture (RSA) in response to nitrogen availability. Overall, this review contributes to identifying recent developments in the interaction between phytohormones and N, as well as serving as a foundation for further study.
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Nitrógeno , Reguladores del Crecimiento de las Plantas , Reguladores del Crecimiento de las Plantas/metabolismo , Nitrógeno/metabolismo , Desarrollo de la Planta/fisiología , Citocininas/metabolismo , Plantas/metabolismo , Raíces de Plantas/metabolismoRESUMEN
High ploids of the sugarcane nuclear genome limit its genomic studies, whereas its chloroplast genome is small and conserved, which is suitable for phylogenetic studies and molecular marker development. Here, we applied whole genome sequencing technology to sequence and assemble chloroplast genomes of eight species of the 'Saccharum Complex', and elucidated their sequence variations. In total, 19 accessions were sequenced, and 23 chloroplast genomes were assembled, including 6 species of Saccharum (among them, S. robustum, S. sinense, and S. barberi firstly reported in this study) and 2 sugarcane relative species, Tripidium arundinaceum and Narenga porphyrocoma. The plastid phylogenetic signal demonstrated that S. officinarum and S. robustum shared a common ancestor, and that the cytoplasmic origins of S. sinense and S. barberi were much more ancient than the S. offcinarum/S. robustum linage. Overall, 14 markers were developed, including 9 InDel markers for distinguishing Saccharum from its relative species, 4 dCAPS markers for distinguishing S. officinarum from S. robustum, and 1 dCAPS marker for distinguishing S. sinense and S. barberi from other species. The results obtained from our studies will contribute to the understanding of the classification and plastome evolution of Saccharinae, and the molecular markers developed have demonstrated their highly discriminatory power in Saccharum and relative species.
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Genoma del Cloroplasto , Saccharum , Genómica/métodos , Filogenia , Poaceae/genética , Saccharum/genéticaRESUMEN
BACKGROUND: Sugarcane (Saccharum) is the most critical sugar crop worldwide. As one of the most enriched transcription factor families in plants, MYB genes display a great potential to contribute to sugarcane improvement by trait modification. We have identified the sugarcane MYB gene family at a whole-genome level through systematic evolution analyses and expression profiling. R2R3-MYB is a large subfamily involved in many plant-specific processes. RESULTS: A total of 202 R2R3-MYB genes (356 alleles) were identified in the polyploid Saccharum spontaneum genomic sequence and classified into 15 subgroups by phylogenetic analysis. The sugarcane MYB family had more members by a comparative analysis in sorghum and significant advantages among most plants, especially grasses. Collinearity analysis revealed that 70% of the SsR2R3-MYB genes had experienced duplication events, logically suggesting the contributors to the MYB gene family expansion. Functional characterization was performed to identify 56 SsR2R3-MYB genes involved in various plant bioprocesses with expression profiling analysis on 60 RNA-seq databases. We identified 22 MYB genes specifically expressed in the stem, of which RT-qPCR validated MYB43, MYB53, MYB65, MYB78, and MYB99. Allelic expression dominance analysis implied the differential expression of alleles might be responsible for the high expression of MYB in the stem. MYB169, MYB181, MYB192 were identified as candidate C4 photosynthetic regulators by C4 expression pattern and robust circadian oscillations. Furthermore, stress expression analysis showed that MYB36, MYB48, MYB54, MYB61 actively responded to drought treatment; 19 and 10 MYB genes were involved in response to the sugarcane pokkah boeng and mosaic disease, respectively. CONCLUSIONS: This is the first report on genome-wide analysis of the MYB gene family in sugarcane. SsMYBs probably played an essential role in stem development and the adaptation of various stress conditions. The results will provide detailed insights and rich resources to understand the functional diversity of MYB transcription factors and facilitate the breeding of essential traits in sugarcane.
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Saccharum , Regulación de la Expresión Génica de las Plantas , Humanos , Filogenia , Fitomejoramiento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Saccharum/genética , Saccharum/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Brain death is the irreversible loss of all the functions of the brain and brainstem. Compared to traditional diagnostic methods of brain death, near-infrared spectroscopy (NIRS) is a noninvasive, objective, cost-effective, and safe way of assessment of brain death. Eighteen brain dead patients and 20 healthy subjects were studied by NIRS, with a multiple-phase protocol at varied fractions of inspired O2 (FIO2). We found that the changes in the concentration ratios of oxyhemoglobin to deoxyhemoglobin (Δ[HbO2]/Δ[Hb]) in the cerebral cortex of brain dead patients were significantly higher than those of healthy subjects, and its low-to-high FIO2 phase was most sensitive, with a recommended threshold in the range 1.40-1.50. Our study indicated that NIRS is a promising technology for assessing brain death. The success of this application potentially offers a supplementary technique for the assessment of brain death in real time in order to be able to promptly offer quality-assured donor organs.
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Muerte Encefálica , Espectroscopía Infrarroja Corta , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Voluntarios Sanos , Hemoglobinas/metabolismo , Humanos , Oxihemoglobinas/metabolismoRESUMEN
Sugarcane is of important economic value for producing sugar and bioethanol. Tripidium arundinaceum (old name: Erianthus arundinaceum) is an intergeneric wild species of sugarcane that has desirable resistance traits for improving sugarcane varieties. However, the scarcity of chromosome markers has hindered the cytogenetic study of T. arundinaceum. Here we applied maize chromosome painting probes (MCPs) to identify chromosomes in sorghum and T. arundinaceum using a repeated fluorescence in situ hybridization (FISH) system. Sequential FISH revealed that these MCPs can be used as reliable chromosome markers for T. arundinaceum, even though T. arundinaceum has diverged from maize over 18 MYs (million years). Using these MCPs, we identified T. arundinaceum chromosomes based on their sequence similarity compared to sorghum and labeled them 1 through 10. Then, the karyotype of T. arundinaceum was established by multiple oligo-FISH. Furthermore, FISH results revealed that 5S rDNA and 35S rDNA are localized on chromosomes 5 and 6, respectively, in T. arundinaceum. Altogether, these results represent an essential step for further cytogenetic research of T. arundinaceum in sugarcane breeding.
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Pintura Cromosómica , Cromosomas de las Plantas/genética , Saccharum/genética , Sondas de ADN/química , Sondas de ADN/genética , FitomejoramientoRESUMEN
It was previously confirmed that the apoptotic and necrotic neurons are found during the acute post-traumatic period, suggesting the induction of apoptosis after traumatic brain injury (TBI). To further explore the involvement of apoptotic factors in TBI, an apoptosis antibody array was conducted to measure the alterations of apoptotic factors in rat brain cortex after TBI. As a result, the Neurological Severity Scale (NSS) scores after TBI were increased, and the cell morphology of the brain cortex was destructed with increased neuronal apoptosis. Furthermore, the caspase-3 activity was increased, and the apoptotic-related factors TNF-α and p53 were up-regulated in the brain cortex. More importantly, in vitro experiments demonstrated that down-regulation of TNF-α in oxygen-glucose deprivation/reoxygenation (OGD/R) cells increased cell viability and decreased apoptosis and the p53 expression. These results suggested the involvement of TNF-α-induced apoptotic signalling pathway by activating p53 in the molecular mechanism of neurological injury.
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Apoptosis , Neuronas/metabolismo , Neuronas/patología , Factor de Necrosis Tumoral alfa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Anticuerpos/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Caspasa 3/metabolismo , Supervivencia Celular , Regulación hacia Abajo , Glucosa/metabolismo , Oxígeno/metabolismo , Interferencia de ARN , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
Traumatic brain injury (TBI) is a dominant cause of death and permanent disability worldwide. Although TBI could significantly increase the proliferation of adult neural stem cells in the hippocampus, the survival and maturation of newborn cells is markedly low. Increasing evidence suggests that the secretome derived from mesenchymal stem cells (MSCs) would be an ideal alternative to MSC transplantation. The successive and microenvironmentally responsive secretion in MSCs may be critical for the functional benefits provided by transplanted MSCs after TBI. Therefore, it is reasonable to hypothesize that the signaling molecules secreted in response to local tissue damage can further facilitate the therapeutic effect of the MSC secretome. To simulate the complex microenvironment in the injured brain well, we used traumatically injured brain tissue extracts to pretreat umbilical cord mesenchymal stem cells (UCMSCs) in vitro and stereotaxically injected the secretome from traumatic injury-preconditioned UCMSCs into the dentate gyrus of the hippocampus in a rat severe TBI model. The results revealed that compared with the normal secretome, the traumatic injury-preconditioned secretome could significantly further promote the differentiation, migration, and maturation of newborn cells in the dentate gyrus and ultimately improve cognitive function after TBI. Cytokine antibody array suggested that the increased benefits of secretome administration were attributable to the newly produced proteins and up-regulated molecules from the MSC secretome preconditioned by a traumatically injured microenvironment. Our study utilized the traumatic injury-preconditioned secretome to amplify neurogenesis and improve cognitive recovery, suggesting this method may be a novel and safer candidate for nerve repair. Cover Image for this issue: doi: 10.1111/jnc.14741.
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Lesiones Traumáticas del Encéfalo/metabolismo , Medios de Cultivo Condicionados/farmacología , Hipocampo/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Neurogénesis/efectos de los fármacos , Animales , Cognición/efectos de los fármacos , Humanos , Ratas , Ratas Sprague-Dawley , Recuperación de la Función/efectos de los fármacos , Cordón UmbilicalRESUMEN
Benapenem is a novel carbapenem. The objective of this study was to determine the pharmacokinetic (PK)/pharmacodynamic (PD) cutoff values and evaluate the optimal administration regimens of benapenem for the treatment of bacterial infections via PK/PD modeling and simulation. Ertapenem was used as a control. Infected mice received an intravenous (i.v.) injection of benapenem or ertapenem of 14.6, 58.4, or 233.6 mg/kg of body weight, and the PK/PD profiles were evaluated. The MICs were determined by using a 2-fold agar dilution method. Mathematical models were developed to characterize the pharmacokinetic profile of benapenem in humans and mice. Monte Carlo simulations were employed to determine the cutoff values and the appropriate benapenem dosing regimens for the treatment of infections caused by clinical isolates of Enterobacteriaceae Two 2-compartment models were developed to describe the PK profiles of benapenem in humans and mice. A two-site binding model was applied to fit the protein binding in mouse plasma. Through correlation analysis, the percentage of the time that the free drug concentration remains above the MIC (%fT>MIC) was determined to be the indicator of efficacy. Results from the simulation showed that the probability of target attainment (PTA) against the tested isolates was over 90% with the dosing regimens studied. The PK/PD cutoff value of benapenem was 1 mg/liter at a %fT>MIC of 60% when given at a dose of 1,000 mg/day by i.v. drip for 0.5 h. The established model provides a better understanding of the pharmacological properties of benapenem for the treatment of Enterobacteriaceae infections. The proposed PK/PD cutoff value suggests that benapenem is a promising antibacterial against the Enterobacteriaceae The cutoff value of 1 mg/liter may be a useful guide for the clinical use of benapenem and for surveillance for benapenem resistance.
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Antibacterianos/farmacocinética , Carbapenémicos/farmacocinética , Desarrollo de Medicamentos , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Modelos Estadísticos , Adulto , Animales , Antibacterianos/sangre , Antibacterianos/farmacología , Área Bajo la Curva , Carbapenémicos/sangre , Carbapenémicos/farmacología , Enterobacter cloacae/efectos de los fármacos , Enterobacter cloacae/crecimiento & desarrollo , Infecciones por Enterobacteriaceae/sangre , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Ertapenem/sangre , Ertapenem/farmacocinética , Ertapenem/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Femenino , Humanos , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/crecimiento & desarrollo , Masculino , Ratones , Ratones Endogámicos ICR , Pruebas de Sensibilidad Microbiana , Método de MontecarloRESUMEN
KEY MESSAGE: A total of 33 additive stem rot QTLs were identified in peanut genome with nine of them consistently detected in multiple years or locations. And 12 pairs of epistatic QTLs were firstly reported for peanut stem rot disease. Stem rot in peanut (Arachis hypogaea) is caused by the Sclerotium rolfsii and can result in great economic loss during production. In this study, a recombinant inbred line population from the cross between NC 3033 (stem rot resistant) and Tifrunner (stem rot susceptible) that consists of 156 lines was genotyped by using 58 K peanut single nucleotide polymorphism (SNP) array and phenotyped for stem rot resistance at multiple locations and in multiple years. A linkage map consisting of 1451 SNPs and 73 simple sequence repeat (SSR) markers was constructed. A total of 33 additive quantitative trait loci (QTLs) for stem rot resistance were detected, and six of them with phenotypic variance explained of over 10% (qSR.A01-2, qSR.A01-5, qSR.A05/B05-1, qSR.A05/B05-2, qSR.A07/B07-1 and qSR.B05-1) can be consistently detected in multiple years or locations. Besides, 12 pairs of QTLs with epistatic (additive × additive) interaction were identified. An additive QTL qSR.A01-2 also with an epistatic effect interacted with a novel locus qSR.B07_1-1 to affect the percentage of asymptomatic plants in a row. A total of 193 candidate genes within 38 stem rot QTLs intervals were annotated with functions of biotic stress resistance such as chitinase, ethylene-responsive transcription factors and pathogenesis-related proteins. The identified stem rot resistance QTLs, candidate genes, along with the associated SNP markers in this study, will benefit peanut molecular breeding programs for improving stem rot resistance.
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Arachis/genética , Mapeo Cromosómico , Resistencia a la Enfermedad/genética , Epistasis Genética , Genes de Plantas , Enfermedades de las Plantas/genética , Tallos de la Planta/microbiología , Sitios de Carácter Cuantitativo/genética , Ascomicetos/fisiología , Ligamiento Genético , Fenotipo , Enfermedades de las Plantas/microbiologíaRESUMEN
Sugarcane (Saccharum spp.) is a highly energy-efficient crop primarily for sugar and bio-ethanol production. Sugarcane genetics and cultivar improvement have been extremely challenging largely due to its complex genomes with high polyploidy levels. In this study, we deeply sequenced the coding regions of 307 sugarcane germplasm accessions. Nearly five million sequence variations were catalogued. The average of 98× sequence depth enabled different allele dosages of sequence variation to be differentiated in this polyploid collection. With selected high-quality genome-wide SNPs, we performed population genomic studies and environmental association analysis. Results illustrated that the ancient sugarcane hybrids, S. barberi and S. sinense, and modern sugarcane hybrids are significantly different in terms of genomic compositions, hybridization processes and their potential ancestry contributors. Linkage disequilibrium (LD) analysis showed a large extent of LD in sugarcane, with 962.4 Kbp, 2739.2 Kbp and 3573.6 Kbp for S. spontaneum, S. officinarum and modern S. hybrids respectively. Candidate selective sweep regions and genes were identified during domestication and historical selection processes of sugarcane in addition to genes associated with environmental variables at the original locations of the collection. This research provided an extensive amount of genomic resources for sugarcane community and the in-depth population genomic analyses shed light on the breeding and evolution history of sugarcane, a highly polyploid species.
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Genoma de Planta/genética , Genómica , Saccharum/genética , Adaptación Fisiológica , Alelos , Quimera , Variación Genética , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple/genética , Poliploidía , Saccharum/fisiologíaRESUMEN
KEY MESSAGE: An Axiom Sugarcane100K SNP array has been designed and successfully utilized to construct the sugarcane genetic map and to identify the QTLs associated with SCYLV resistance. To accelerate genetic studies in sugarcane, an Axiom Sugarcane100K single-nucleotide polymorphism (SNP) array was designed and customized in this study. Target enrichment sequencing 300 sugarcane accessions selected from the world collection of sugarcane and related grass species yielded more than four million SNPs, from which a total of 31,449 single-dose (SD) SNPs and 68,648 low-dosage (33,277 SD and 35,371 double dose) SNPs from two datasets, respectively, were selected and tiled on Affymetrix Axiom SNP array. Most of selected SNPs (91.77%) were located within genic regions (12,935 genes), with an average of 7.1 SNPs/gene according to sorghum gene models. This array was used to genotype 469 sugarcane clones, including one F1 population derived from the cross between Green German and IND81-146, one selfing population derived from CP80-1827, and 11 diverse sugarcane accessions as controls. Results of genotyping revealed a high polymorphic SNP rate (77.04%) among the 469 samples. Three linkage maps were constructed by using SD SNP markers, including a genetic map for Green German with 3482 SD SNP markers spanning 3336 cM, a map for IND81-146 with 1513 SD SNP markers spanning 2615 cM, and a map for CP80-1827 with 536 SD SNP markers spanning 3651 cM. Quantitative trait loci (QTL) analysis identified 18 QTLs controlling Sugarcane yellow leaf virus resistance segregating in the two mapping populations, harboring 27 disease-resistant genes. This study demonstrated the successful development and utilization of a SNP array as an efficient genetic tool for high-throughput genotyping in highly polyploid sugarcane.
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Mapeo Cromosómico/métodos , Ligamiento Genético , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Saccharum/genética , Genoma de Planta , Genotipo , Técnicas de Genotipaje , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
Sugarcane (Saccharum spp.) supplies globally â¼80% of table sugar and 60% of bioethanol. Sugarcane orange rust and Sugarcane yellow leaf virus (SCYLV) are major sugarcane diseases, causing up to 50 and 40% yield losses, respectively. Sugarcane cultivars resistant to these diseases are needed to sustain sugarcane production in several regions. Dissecting DNA sequence variants controlling disease resistance provides a valuable tool for fulfilling a breeding strategy to develop resistant cultivars. In this study, we evaluated disease reactions to orange rust and SCYLV of a sugarcane diversity panel in repeated trials. We conducted a genome-wide association study between high-density markers and disease resistance reactions. We identified 91 putative DNA markers and 82 candidate genes significantly associated with resistance to one of the two diseases. These provide an important genetic resource for finding genes and molecular markers for disease resistance. Our results emphasized the importance of utilizing a wide germplasm collection for breeding resistant sugarcane cultivars.