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Phylogenetic tree inference is a classic fundamental task in evolutionary biology that entails inferring the evolutionary relationship of targets based on multiple sequence alignment (MSA). Maximum likelihood (ML) and Bayesian inference (BI) methods have dominated phylogenetic tree inference for many years, but BI is too slow to handle a large number of sequences. Recently, deep learning (DL) has been successfully applied to quartet phylogenetic tree inference and tentatively extended into more sequences with the quartet puzzling algorithm. However, no DL-based tools are immediately available for practical real-world applications. In this paper, we propose Fusang (http://fusang.cibr.ac.cn), a DL-based framework that achieves comparable performance to that of ML-based tools with both simulated and real datasets. More importantly, with continuous optimization, e.g. through the use of customized training datasets for real-world scenarios, Fusang has great potential to outperform ML-based tools.
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Aprendizaje Profundo , Filogenia , Algoritmos , Teorema de Bayes , Alineación de Secuencia , Funciones de VerosimilitudRESUMEN
Phonons are known to generate a thermal Hall effect in certain insulators, including oxides with rare-earth impurities, quantum paraelectrics, multiferroic materials, and cuprate Mott insulators. In each case, a special feature of the material is presumed relevant for the underlying mechanism that confers chirality to phonons in a magnetic field. A fundamental question is whether a phonon Hall effect is an unusual occurrence-linked to special characteristics such as skew scattering off rare-earth impurities, structural domains, ferroelectricity, or ferromagnetism-or a much more common property of insulators than hitherto believed. To help answer this question, we have turned to a material with none of the previously encountered special features: the cubic antiferromagnet Cu3TeO6. We find that its thermal Hall conductivity [Formula: see text] is among the largest of any insulator so far. We show that this record-high [Formula: see text] signal is due to phonons, and it does not require the presence of magnetic order, as it persists above the ordering temperature. We conclude that the phonon Hall effect is likely to be a fairly common property of solids.
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The structure of solvated Li+ has a significant influence on the electrolyte/electrode interphase (EEI) components and desolvation energy barrier, which are two key factors in determining the Li+ diffusion kinetics in lithium metal batteries. Herein, the "solvent activity" concept is proposed to quantitatively describe the correlation between the electrolyte elements and the structure of solvated Li+. Through fitting the correlation of the electrode potential and solvent concentration, we suggest a "low-activity-solvent" electrolyte (LASE) system for deriving a stable inorganic-rich EEI. Nano LiF particles, as a model, were used to capture free solvent molecules for the formation of a LASE system. This advanced LASE not only exhibits outstanding antidendrite growth behavior but also delivers an impressive performance in Li/LiNi0.8Co0.1Mn0.1O2 cells (a capacity of 169 mAh g-1 after 250 cycles at 0.5 C).
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In this paper, a 1 × 2 photonic switch is designed based on a silicon-on-insulator (SOI) platform combined with the phase change material (PCM), Sb2S3, assisted by the direct binary search (DBS) algorithm. The designed photonic switch exhibits an impressive operating bandwidth ranging from 1450 to 1650 nm. The device has an insertion loss (IL) from 0.44 dB to 0.70 dB (of less than 0.7 dB) and cross talk (CT) from -26 dB to -20 dB (of less than -20 dB) over an operating bandwidth of 200 nm, especially an IL of 0.52 dB and CT of -24 dB at 1550 nm. Notably, the device is highly compact, with footprints of merely 3 × 4 µm2. Furthermore, we have extended the device's functionality for multifunctional operation in the C-band that can serve as both a 1 × 2 photonic switch and a 3 dB photonic power splitter. In the photonic switch mode, the device demonstrates an IL of 0.7 dB and a CT of -13.5 dB. In addition, when operating as a 3 dB photonic power splitter, the IL is less than 0.5 dB.
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The stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) are frequently used for the treatment of attention-deficit/hyperactivity disorder (ADHD); however, the function of these drugs in different types of brain cells and their effects on related genes remain largely unknown. To address these questions, we built a pipeline for the simultaneous examination of the activity behavior and transcriptional responses of Drosophila melanogaster at single-cell resolution following drug treatment. We selected the Drosophila with significantly increased locomotor activities (hyperactivity-like behavior) following the administration of each drug in comparison with the control (same food as the drug-treated groups with 5% sucrose, yeast, and blue food dye solution) using EasyFlyTracker. Subsequently, single cell RNA sequencing (scRNASEQ) was used to capture the transcriptome of 82,917 cells, unsupervised clustering analysis of which yielded 28 primary cell clusters representing the major cell types in adult Drosophila brain. Indeed, both neuronal and glial cells responded to MPH and ATX. Further analysis of differentially expressed genes (DEGs) revealed distinct transcriptional changes associated with these two drugs, such as two well-studied dopamine receptor genes (Dop2R and DopEcR) were responsive to MPH but not to ATX at their optimal doses, in addition to genes involved in dopamine metabolism pathways such as Syt1, Sytalpha, Syt7, and Ih in different cell types. More importantly, MPH also suppressed the expression of genes encoding other neurotransmitter receptors and synaptic signaling molecules in many cell types, especially those for Glu and GABA, while the responsive effects of ATX were much weaker. In addition to monoaminergic neuronal transmitters, other neurotransmitters have also shown a similar pattern with respect to a stronger effect associated with MPH than with ATX. Moreover, we identified four distinct glial cell subtypes responsive to the two drugs and detected a greater number of differentially expressed genes associated with ensheathing and astrocyte-like glia. Furthermore, our study provides a rich resource of candidate target genes, supported by drug set enrichment analysis (P = 2.10E-4; hypergeometric test), for the further exploration of drug repurposing. The whole list of candidates can be found at ADHDrug ( http://adhdrug.cibr.ac.cn/ ). In conclusion, we propose a fast and cost-efficient pipeline to explore the underlying molecular mechanisms of ADHD drug treatment in Drosophila brain at single-cell resolution, which may further facilitate drug repurposing applications.
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BACKGROUND: Abnormal activation of FAK is associated with tumor development and metastasis. Through interactions with other intracellular signalling molecules, FAK influences cytoskeletal remodelling, modulation of adhesion signalling, and activation of transcription factors, promoting migration and invasion of tumor cells. However, the exact mechanism that regulates these processes remains unresolved. Herein, our findings indicate that the S-palmitoylation of FAK is crucial for both its membrane localization and activation. METHODS: The palmitoylation of FAK in U251 and T98G cells was assessed by an acyl-PEG exchange (APE) assay and a metabolic incorporation assay. Cellular palmitoylation was inhibited using 2-bromopalmitate, and the palmitoylation status and cellular localization of FAK were determined. A metabolic incorporation assay was used to identify the potential palmitoyl acyltransferase and the palmitoylation site of FAK. Cell Counting Kit-8 (CCK8) assays, colony formation assays, and Transwell assays were conducted to assess the impact of ZDHHC5 in GBM. Additionally, intracranial GBM xenografts were utilized to investigate the effects of genetically silencing ZDHHC5 on tumor growth. RESULTS: Inhibiting FAK palmitoylation leads to its redistribution from the membrane to the cytoplasm and a decrease in its phosphorylation. Moreover, ZDHHC5, a protein-acyl-transferase (PAT), catalyzes this key modification of FAK at C456. Knockdown of ZDHHC5 abrogates the S-palmitoylation and membrane distribution of FAK and impairs cell proliferation, invasion, and epithelial-mesenchymal transition (EMT). Taken together, our research reveals the crucial role of ZDHHC5 as a PAT responsible for FAK S-palmitoylation, membrane localization, and activation. CONCLUSIONS: These results imply that targeting the ZDHHC5/FAK axis has the potential to be a promising strategy for therapeutic interventions for glioblastoma (GBM). Video Abstract.
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Glioblastoma , Glioma , Humanos , Línea Celular Tumoral , Movimiento Celular , Transición Epitelial-Mesenquimal , Glioblastoma/metabolismo , Glioma/patología , Lipoilación , Transducción de SeñalRESUMEN
In recent decades, nucleic acid self-assemblies have emerged as popular nanomaterials due to their programmable and robust assembly, prescribed geometry, and versatile functionality. However, it remains a challenge to purify large quantities of DNA nanostructures or DNA-templated nanocomplexes for various applications. Commonly used purification methods are either limited by a small scale or incompatible with functionalized structures. To address this unmet need, we present a robust and scalable method of purifying DNA nanostructures by Sepharose resin-based size exclusion. The resin column can be manually packed in-house with reusability. The separation is driven by a low-pressure gravity flow in which large DNA nanostructures are eluted first followed by smaller impurities of ssDNA and proteins. We demonstrated the efficiency of the method for purifying DNA origami assemblies and protein-immobilized DNA nanostructures. Compared to routine agarose gel electrophoresis that yields 1 µg or less of purified products, this method can purify â¼100-1000 µg of DNA nanostructures in less than 30 min, with the overall collection yield of 50-70% of crude preparation mixture. The purified nanocomplexes showed more precise activity in evaluating enzyme functions and antibody-triggered activation of complement protein reactions.
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Biosensors are currently among the most commonly used devices for analysing biomarkers and play an important role in environmental detection, food safety, and disease diagnosis. Researchers have developed multimodal biosensors instead of single-modal biosensors to meet increasing sensitivity, accuracy, and stability requirements. Metal nanoparticles (MNPs) are beneficial for preparing core probes for multimodal biosensors because of their excellent physical and chemical properties, such as easy regulation and modification, and because they can integrate diverse sensing strategies. This review mainly summarizes the excellent physicochemical properties of MNPs applied as biosensing probes and the principles of commonly used MNP-based multimodal sensing strategies. Recent applications and possible improvements of multimodal biosensors based on MNPs are also described, among which on-site inspection and sensitive detection are particularly important. The current challenges and prospects for multimodal biosensors based on MNPs may provide readers with a new perspective on this field.
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Técnicas Biosensibles , Nanopartículas del Metal , Técnicas Biosensibles/métodos , Nanopartículas del Metal/química , HumanosRESUMEN
BACKGROUND: The study aimed to investigate the relationship of MAPK4 genetic variants with the efficacy of methotrexate (MTX) in psoriasis patients. METHODS: Patients treated with MTX were classified as responders or nonresponders if the Psoriasis Area and Severity Index (PASI) at week 12 was reduced to greater than 75% or lower than 75%, respectively. The genotypes of 14 MAPK4 single-nucleotide polymorphisms in 310 patients were analyzed. The expression levels of MAPK4 protein were detected by Western blot. RESULTS: Only rs9949644 polymorphisms were associated with the efficacy after adjusting for the confounding factors. Patients with the rs9949644 AG or GG genotype had a better clinical response compared to patients with the AA genotype. Rs9949644 polymorphisms were significantly associated with the PASI improvement rate. Besides, the protein level of MAPK4, positively associated with the psoriasis severity, was higher in patients. There were no significant differences of MAPK4 protein levels among the three groups. While after treatment, MAPK4 levels in the AG or GG group showed a significantly down-regulated trend. CONCLUSION: By demonstrating the significant association of MAPK4 with the efficacy of MTX, this study indicates that MAPK4 may be involved in the psoriasis progression and act as a predictor of therapeutic response.
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Fármacos Dermatológicos , Psoriasis , Humanos , Metotrexato/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Resultado del Tratamiento , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Psoriasis/inducido químicamente , Polimorfismo de Nucleótido SimpleRESUMEN
In this work, the threshold photoionization cross sections from the excited states of lutetium and ytterbium atoms were investigated by the laser pump-probe scheme under the condition of saturated resonant excitation. We obtained the resonance enhanced multiphoton ionization spectra of the lutetium and ytterbium atoms of the lanthanide metals in the range of 307.50-312.50 nm and 265.00-269.00 nm, respectively; the photoionization cross sections of the 5d6s(1D)6p(2D05/2) and 5d6s(3D)6p(2P01/2) states of lutetium and the 4f13(2F0)5d6s2(J = 1) states of ytterbium above threshold regions (0.4-1.6 eV) were measured, and measured values ranged from 2.3 ± 0.2 to 17.7 ± 1.5 Mb.
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In this paper, an age-structured predator-prey system with Beddington-DeAngelis (B-D) type functional response, prey refuge and harvesting is investigated, where the predator fertility function f(a) and the maturation function ß ( a ) are assumed to be piecewise functions related to their maturation period τ . Firstly, we rewrite the original system as a non-densely defined abstract Cauchy problem and show the existence of solutions. In particular, we discuss the existence and uniqueness of a positive equilibrium of the system. Secondly, we consider the maturation period τ as a bifurcation parameter and show the existence of Hopf bifurcation at the positive equilibrium by applying the integrated semigroup theory and Hopf bifurcation theorem. Moreover, the direction of Hopf bifurcation and the stability of bifurcating periodic solutions are studied by applying the center manifold theorem and normal form theory. Finally, some numerical simulations are given to illustrate of the theoretical results and a brief discussion is presented.
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FertilidadRESUMEN
As agents in an emerging technology, Hermetia illucens (Linnaeus, 1758) (Diptera: Stratiomyidae) larvae, black soldier fly, have shown exciting potential for degrading antibiotics in organic solid waste, a process for which gut microorganisms play an important role. This study investigated the characteristics of larval gut bacterial communities effected by typical antibiotics. Initially, antibiotics significantly reduced the diversity of gut bacterial species. After 8 days, diversity recovered to similar to that of the control group in the chlortetracycline, tylosin, and sulfamethoxazole groups. Proteobacteria, Firmicutes, and Actinobacteriota were the dominant phyla at the initial BSFL gut. However, after 4 days treatment, the proportion of Actinobacteriota significantly decreased, but Bacteroidota notably increased. During the conversion process, 18, 18, 17, 21, and 19 core genera were present in the chlortetracycline, sulfamethoxazole, tylosin, norfloxacin, and gentamicin groups, respectively. Pseudomonas, Actinomyces, Morganella, Providencia and Klebsiella might be the important genera with extraordinary resistance and degradation to antibiotics. Statistical analyses of COGs showed that antibiotics changed the microbial community functions of BSFL gut. Compared with the control group, (i) the chlortetracycline, sulfamethoxazole, and tylosin groups showed significant increase in the classification functions of transcription, RNA processing and modificationï¼and so on, (ii) the norfloxacin and gentamicin groups showed significant increase in defense mechanisms and other functions. Note that we categorized the response mechanisms of these classification functions to antibiotics into resistance and degradation. This provides a new perspective to deeply understand the joint biodegradation behavior of antibiotics in environments, and serves as an important reference for further development and utilization of microorganisms-assisted larvae for efficient degradation of antibiotics.
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Clortetraciclina , Dípteros , Microbioma Gastrointestinal , Animales , Dípteros/fisiología , Larva , Antibacterianos/farmacología , Norfloxacino , Tilosina , Bacterias , Sulfametoxazol , GentamicinasRESUMEN
Digital industrialization represented by big data provides substantial support for the high-quality development of the digital economy, but its impact on urban energy conservation development requires further research. To this end, based on the panel data of Chinese cities from 2010 to 2019 and taking the establishment of the national big data comprehensive pilot zone (NBDCPZ) as a quasi-natural experiment, this paper explores the impact, mechanism, and spatial spillover effect of digital industrialization represented by big data on urban energy conservation development using the Difference-in-Differences (DID) method. The results show that digital industrialization can help achieve urban energy conservation development, which still holds after a series of robustness tests. Mechanism analysis reveals that digital industrialization impacts urban energy conservation development by driving industrial sector output growth, promoting industrial upgrading, stimulating green technology innovation, and alleviating resource misallocation. Heterogeneity analysis indicates that the energy conservation effect of digital industrialization is more significant in the central region, intra-regional demonstration comprehensive pilot zones, large cities, non-resource-based cities, and high-level digital infrastructure cities. Additionally, digital industrialization can promote energy conservation development in neighboring areas through spatial spillover effect. This paper enriches the theoretical framework concerning the relationship between digital industrialization and energy conservation development. The findings have significant implications for achieving the coordinated development of digitalization and conservation.
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BACKGROUND: Environmental changes are expected to intensify in the future. The invasion of toxic plants under environmental changes may change herbivore feeding environments. Herbivores living long-term in toxic plant-feeding environments will inevitably ingest plant secondary metabolites (PSMs), and under different feeding environments are likely to have unique protection mechanisms that support improved adaptation to PSMs in their habitat. We aimed to compare different subterranean herbivore population responses and adaptations to toxic plants to unveil their feeding challenges. RESULTS: Here, we investigated the adaptive capacity of the liver in two geographically separated populations of plateau zokors (Eospalax baileyi) before and after exposure to the toxic plant Stellera chamaejasme (SC), at the organ, biochemical, and transcriptomic levels. The results showed no significant liver granules or inflammatory reactions in the Tianzhu (TZ) population after the SC treatment. The transaminase level in the TZ population was significantly lower than that in the Luqu population. Transcriptome analysis revealed that the TZ population exhibited interactions with other detoxification metabolic pathways by oxytocin pathway-associated genes, including diacylglycerol lipase alpha (Dagla), calcium/calmodulin dependent protein kinase II Alpha (Camk2a), and CD38 molecule (Cd38). The phase II process of liver drug metabolism increased to promote the rate of metabolism. We found that alternative splicing (AS) and the expression of the cyclin D (Ccnd1) gene interact-a TZ population hallmark-reduced liver inflammatory responses. CONCLUSION: Our study supports the detoxification limitation hypothesis that differences in liver detoxification metabolism gene expression and AS are potential factors in herbivore adaptation to PSMs and may be a strategy of different herbivore populations to improve toxic plant adaptability.
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Plantas Tóxicas , Transcriptoma , Hígado , Perfilación de la Expresión Génica , AclimataciónRESUMEN
Investigation on the interactions between enantiomers of chiral drugs and biomolecules can help precisely understand their biological behaviors in vivo and provide insights into the design of new drugs. Herein, we designed and synthesized a pair of optically pure, cationic, double-stranded dinuclear Ir(III)-metallohelices (Λ2R4-H and Δ2S4-H), and their dramatic enantiomer-dependent photodynamic therapy (PDT) responses were thoroughly studied in vitro and in vivo. Compared to the mononuclear enantiomeric or racemic [Ir(ppy)2(dppz)][PF6] (Λ-/Δ-Ir, rac-Ir) that with high dark toxicity and low photocytotoxicity index (PI) values, both of the optically pure metallohelices displayed negligible toxicity in the dark while exhibiting very distinctive light toxicity upon light irradiation. The PI value of Λ2R4-H was approximately 428, however, Δ2S4-H significantly reached 63,966. Interestingly, only Δ2S4-H was found to migrate from mitochondria to nucleus after light irradiation. Further proteomic analysis verified that Δ2S4-H activated the ATP-dependent migration process after light irradiation, and subsequently inhibited the activities of the nuclear proteins such as superoxide dismutase 1 (SOD1) and eukaryotic translation initiation factor 5A (EIF5A) to trigger the accumulation of superoxide anions and downregulate mRNA splicing processes. Molecular docking simulations suggested that the interactions between metallohelices and nuclear pore complex NDC1 dominated the migration process. This work presents a new kind of Ir(III) metallohelices-based agent with the highest PDT efficacy, highlights the importance of metallohelices' chirality, and provides inspirations for the future design of chiral helical metallodrugs.
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Núcleo Celular , Proteómica , Simulación del Acoplamiento Molecular , Estereoisomerismo , IridioRESUMEN
Li||NMC811 battery, with lithium-metal (high specific capacity and low redox potential) as anode and LiNi0.8 Co0.1 Mn0.1 O2 (NMC811) as cathode, has been widely accepted to be a good candidate as one of the high-energy-density batteries. However, its cyclability needs improvement to fulfill the requirement for its future commercial use, especially under practical conditions. Electrolyte plays a key role in improving the cycling performance of Li||NMC811 batteries, where a high voltage/electrochemical window and good stability with the electrodes of the electrolyte are required. Herein, a localized high-concentration electrolyte with an additive of lithium difluoro(oxalate)borate (LiDFOB) is reported that improves the cycling performance of Li||NMC811 cells under crucial conditions with Li foil thickness of 50 µm, cathode areal loading of 4 mAh cm-2 , the areal capacity ratio between the negative and positive electrodes (N/P ratio) of 2.6 and the electrolyte/cell capacity ratio (E/C ratio) of 3.0 g (Ah)-1 . These cells can maintain 80% of the capacity after 195 cycles.
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In the system of magnesium-loaded scaffolds, the effect of magnesium ions (Mg2+ ) on the osteogenesis induction is restricted due to the low transmembrane transport efficiency of Mg2+ into the cell, which limits the application for bone defect repair. Inspired by the fact that magnetic field can regulate ion channel proteins on the cell membrane, magnetite nanoparticle is introduced into the poly (l-lactic acid) /magnesium oxide composite in this study, and a magnetic magnesium-loaded bone scaffold is prepared via selective laser sintering . Notably, the activities of the Mg2+ channel protein (MAGT1) on the membrane of bone marrow mesenchymal stem cells (rBMSCs) are enhanced via magnetic torque effect (via integrin αV ß3/actin), under the action of static magnetic field (SMF), which promoted rBMSCs to capture Mg2+ in the microenvironment and induced osteogenesis. In vitro experiments showed that the magnetic magnesium-loaded scaffold, under the action of SMF, can accelerate the inflow of Mg2+ from surrounding microenvironment, which improved cellular activities, osteogenesis-related gene expression (ALP, Runx2, OCN, and OPN), and mineralization. Besides, in vivo skull defect repair experiments showed that the scaffolds possessed good ability to promote bone differentiation and new bone regeneration.
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Magnesio , Andamios del Tejido , Magnesio/farmacología , Osteogénesis , Regeneración Ósea , Cráneo , Diferenciación Celular , Iones , Campos Magnéticos , Ingeniería de TejidosRESUMEN
High-energy-density Li metal batteries (LMBs) with Nickel (Ni)-rich cathode and Li-metal anode have attracted extensive attention in recent years. However, commercial carbonate electrolytes bring severe challenges including poor cycling stability, severe Li dendrite growth and cathode cracks, and narrow operating temperature window, especially hardly work at below -40 °C. In this work, a 2.4 m lithium difluoro(oxalato)borate (LiDFOB) in ethyl acetate (EA) solvent with 20 wt% fluorocarbonate (FEC) (named 2.4m-DEF) is designed to solve Li+ transport dynamic at low temperature and improve interfacial stability between electrolyte with Li anode or Ni-rich cathode. Beneficial lower freezing point, lower viscosity, and higher dielectric constant of EA solvent, the electrolyte exhibits excellent Li+ transport dynamic. Relying on the unique Li+ solvation structure, more DFOB- anions and FEC solvents are decomposed to establish a stable solid electrolyte interface at electrolyte/electrode. Therefore, LiNi0.9 Co0.05 Mn0.05 O2 (NCM90)/Li LMB with 2.4m-DEF enables excellent rate capability (184 mA h g-1 at 30 C) and stable cycling performance with ≈93.7% of capacity retention after 200 cycles at 20 C and room temperature. Moreover, the NCM90/Li LMB with 2.4m-DEF exhibits surprising ultra-low-temperature performance, showing 173 mA h g-1 at -40 °C and 152 mA h g-1 at -60 °C, respectively.
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MAIN CONCLUSION: Phytophthora infestans effectors manipulate the antagonism of host hormones to interfere with the immune response of plants at different infection stages. Phytophthora infestans (P. infestans) poses a serious threat to global crop production, and its effectors play an indispensable role in its pathogenicity. However, the function of these effectors during the switch from biotrophy to necrotrophy of P. infestans remains unclear. Further research on the effectors that manipulate the antagonistic response of host hormones is also lacking. In this study, a coexpression analysis and infection assays were performed to identify distinct gene expression changes in both P. infestans and tomato. During the switch from biotrophy to necrotrophy, P. infestans secretes three types of effectors to interfere with host salicylic acid (SA), jasmonic acid (JA), ethylene (ET), and abscisic acid (ABA) levels. The three aforementioned effectors also regulate the host gene expression including NPR1, TGA2.1, PDF1.2, NDR1, ERF3, NCED6, GAI4, which are involved in hormone crosstalk. The changes in plant hormones are mediated by the three types of effectors, which may accelerate infection and drive completion of the P. infestans lifecycle. Our findings provide new insight into plantâpathogen interactions that may contribute to the prevention growth of hemibiotrophic pathogens.
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Phytophthora infestans , Reguladores del Crecimiento de las Plantas/metabolismo , Transducción de Señal , Ácido Salicílico/metabolismo , Hormonas/metabolismo , Enfermedades de las PlantasRESUMEN
A large amount of omics data and number of bioinformatics tools has been produced. However, the methods for further exploring omics data are simple, in particular, to mine key regulatory genes, which are a priority concern in biological systems, and most of the specific functions are still unknown. First, raw data of two genotypes of melon (susceptible and resistant) were obtained by transcriptome analysis. Second, 391 transcription factors (TFs) were identified from the plant transcription factor database and cucurbit genomics database. Then, functional enrichment analysis indicated that these genes were mainly annotated in the process of transcription regulation. Third, 243 and 230 module-specific TFs were screened by weighted gene coexpression network analysis and short time series expression miner, respectively. Several TF genes, such as WRKYs and bHLHs, were regarded as key regulatory genes according to the values of significantly different modules. The coexpression network showed that these TF genes were significant correlated with resistance (R) genes, such as DRP2, RGA3, DRP1 and NB-ARC. Fourth, cis-acting element analysis illustrated that these R genes may bind to WRKY and bHLH. Finally, the expression of WRKY genes was verified by quantitative reverse transcription PCR (RT-qPCR). Phylogenetic analysis was carried out to further confirm that these TFs may play a critical role in Curcurbitaceae disease resistance. This study provides a new optimized combination strategy to explore the functions of TFs in a wide spectrum of biological processes. This strategy may also effectively predict potential relationships in the interactions of essential genes.