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KEY MESSAGE: The Dof22 gene encoding a deoxyribonucleic acid binding with one finger in maize, which is associated with its drought tolerance. The identification of drought stress regulatory genes is essential for the genetic improvement of maize yield. Deoxyribonucleic acid binding with one finger (Dof), a plant-specific transcription factor family, is involved in signal transduction, morphogenesis, and environmental stress responses. In present study, by weighted correlation network analysis (WGCNA) and gene co-expression network analysis, 15 putative Dof genes were identified from maize that respond to drought and rewatering. A real-time fluorescence quantitative PCR showed that these 15 genes were strongly induced by drought and ABA treatment, and among them ZmDof22 was highly induced by drought and ABA treatment. Its expression level increased by nearly 200 times after drought stress and more than 50 times after ABA treatment. After the normal conditions were restored, the expression levels were nearly 100 times and 40 times of those before treatment, respectively. The Gal4-LexA/UAS system and transcriptional activation analysis indicate that ZmDof22 is a transcriptional activator regulating drought tolerance and recovery ability in maize. Further, overexpressed transgenic and mutant plants of ZmDof22 by CRISPR/Cas9, indicates that the ZmDof22, improves maize drought tolerance by promoting stomatal closure, reduces water loss, and enhances antioxidant enzyme activity by participating in the ABA pathways. Taken together, our findings laid a foundation for further functional studies of the ZmDof gene family and provided insights into the role of the ZmDof22 regulatory network in controlling drought tolerance and recovery ability of maize.
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Sequías , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Estomas de Plantas , Factores de Transcripción , Zea mays , Zea mays/genética , Zea mays/fisiología , Zea mays/enzimología , Estomas de Plantas/fisiología , Estomas de Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Estrés Fisiológico/genética , Antioxidantes/metabolismo , Plantas Modificadas Genéticamente/genética , Ácido Abscísico/metabolismo , Resistencia a la SequíaRESUMEN
BACKGROUND: Slow kVp switching technique is an important approach to realize dual-energy CT (DECT) imaging, but its performance has not been thoroughly investigated yet. OBJECTIVE: This study aims at comparing and evaluating the DECT imaging performance of different slow kVp switching protocols, and thus helps determining the optimal system settings. METHODS: To investigate the impact of energy separation, two different beam filtration schemes are compared: the stationary beam filtration and dynamic beam filtration. Moreover, uniform tube voltage modulation and weighted tube voltage modulation are compared along with various modulation frequencies. A model-based direct decomposition algorithm is employed to generate the water and iodine material bases. Both numerical and physical experiments are conducted to verify the slow kVp switching DECT imaging performance. RESULTS: Numerical and experimental results demonstrate that the material decomposition is less sensitive to beam filtration, voltage modulation type and modulation frequency. As a result, robust material-specific quantitative decomposition can be achieved in slow kVp switching DECT imaging. CONCLUSIONS: Quantitative DECT imaging can be implemented with slow kVp switching under a variety of system settings.
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Yodo , Tomografía Computarizada por Rayos X , Fantasmas de Imagen , Tomografía Computarizada por Rayos X/métodos , AlgoritmosRESUMEN
Both hemispheres connect with each other by excitatory callosal projections, and whether inhibitory interneurons, usually believed to have local innervation, engage in transcallosal activity modulation is unknown. Here, we used optogenetics in combination with cell-type-specific channelrhodopsin-2 expression to activate different inhibitory neuron subpopulations in the visual cortex and recorded the response of the entire visual cortex using intrinsic signal optical imaging. We found that optogenetic stimulation of inhibitory neurons reduced spontaneous activity (increase in the reflection of illumination) in the binocular area of the contralateral hemisphere, although these stimulations had different local effects ipsilaterally. The activation of contralateral interneurons differentially affected both eye responses to visual stimuli and, thus, changed ocular dominance. Optogenetic silencing of excitatory neurons affects the ipsilateral eye response and ocular dominance in the contralateral cortex to a lesser extent. Our results revealed a transcallosal effect of interneuron activation in the mouse visual cortex.
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Predominio Ocular , Corteza Visual , Animales , Ratones , Corteza Visual/fisiología , Neuronas/fisiología , Interneuronas/fisiologíaRESUMEN
Zinc oxide nanoparticles (ZnO NPs) have exhibited excellent anti-tumor properties; the present study aimed to elucidate the underlying mechanism of ZnO NPs induced apoptosis in acute myeloid leukemia (AML) cells by regulating mitochondrial division. THP-1 cells, an AML cell line, were first incubated with different concentrations of ZnO NPs for 24 hr. Next, the expression of Drp-1, Bcl-2, Bax mRNA, and protein was detected, and the effects of ZnO NPs on the levels of reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), apoptosis, and ATP generation in THP-1 cells were measured. Moreover, the effect of Drp-1 inhibitor Mdivi-1 and ZnO NPs on THP-1 cells was also detected. The results showed that the THP-1 cells survival rate decreased with the increment of ZnO NPs concentration and incubation time in a dose- and time-dependent manner. ZnO NPs can reduce the cell Δψm and ATP levels, induce ROS production, and increase the levels of mitochondrial division and apoptosis. In contrast, the apoptotic level was significantly reduced after intervention of Drp-1 inhibitor, suggesting that ZnO NPs can induce the apoptosis of THP-1 cells by regulating mitochondrial division. Overall, ZnO NPs may provide a new basis and idea for treating human acute myeloid leukemia in clinical practice.
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Leucemia Mieloide Aguda , Nanopartículas , Óxido de Zinc , Adenosina Trifosfato/metabolismo , Apoptosis , Supervivencia Celular , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Óxido de Zinc/farmacologíaRESUMEN
In many clinical trials, outcomes of interest are binary-valued. It is not uncommon that a binary-valued outcome is dichotomized from a continuous outcome at a threshold of clinical interest. To analyze such data, common approaches include (a) fitting a generalized linear mixed model (GLMM) to the dichotomized longitudinal binary outcome; and (b) the multiple imputation (MI) based method: imputing missing values in the continuous outcome, dichotomizing it into a binary outcome, and then fitting a generalized linear model to the "complete" data. We conducted comprehensive simulation studies to compare the performance of the GLMM versus the MI-based method for estimating the risk difference and the logarithm of odds ratio between two treatment arms at the end of study. In those simulation studies, we considered a range of multivariate distribution options for the continuous outcome (including a multivariate normal distribution, a multivariate t-distribution, a multivariate log-normal distribution, and the empirical distribution from a real clinical trial data) to evaluate the robustness of the estimators to various data-generating models. Simulation results demonstrate that both methods work well under those considered distribution options, but the MI-based method is more efficient with smaller mean squared errors compared to the GLMM. We further applied both the GLMM and the MI-based method to 29 phase 3 diabetes clinical trials, and found that the MI-based method generally led to smaller variance estimates compared to the GLMM.
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Interpretación Estadística de Datos , Simulación por Computador , Humanos , Modelos Lineales , Distribución NormalRESUMEN
The apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G) converts cytosine to uracil in DNA/RNA. Its role in resisting viral invasion has been well documented. However, its expression pattern and potential function in AML remain unclear. In this study, we carried out a bioinformatics analysis and revealed that the expression of APOBEC3G was significantly upregulated in AML, and high expression of APOBEC3G was significantly associated with short overall survival (OS). APOBEC3G expression was especially increased in non-M3AML, and correlated with the unfavorable cytogenetic risks. Additionally, Cox regression analyses indicated APOBEC3G is a hazard factor that cannot be ignored for OS of AML patients. In molecular docking simulations, the natural product crotonoside was found to interact well with APOBEC3G. The expression of APOBEC3G is the highest in KG-1 cells, and the treatment with crotonoside can reduce the expression of APOBEC3G. Crotonoside can inhibit the viability of different AML cells in vitro, arrest KG-1 and MV-4-11 cells in the S phase of the cell cycle and affect the expression of cycle-related proteins, and induce cell apoptosis. Therefore, APOBEC3G could be a potential drug target of crotonoside, and crotonoside can be considered as a lead compound for APOBEC3G inhibition in non-M3 AML.
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Productos Biológicos , VIH-1 , Leucemia Mieloide Aguda , Desaminasas APOBEC-1 , Desaminasa APOBEC-3G/genética , Adenosina , Biomarcadores , Citidina Desaminasa/genética , Citidina Desaminasa/metabolismo , Citosina , Guanosina , VIH-1/genética , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Simulación del Acoplamiento Molecular , Pronóstico , ARN , UraciloRESUMEN
BACKGROUND: Maize (Zea mays) ear length, which is an important yield component, exhibits strong heterosis. Understanding the potential molecular mechanisms of ear-length heterosis is critical for efficient yield-related breeding. RESULTS: Here, a joint netted pattern, including six parent-hybrid triplets, was designed on the basis of two maize lines harboring long (T121 line) and short (T126 line) ears. Global transcriptional profiling of young ears (containing meristem) was performed. Multiple comparative analyses revealed that 874 differentially expressed genes are mainly responsible for the ear-length variation between T121 and T126 lines. Among them, four key genes, Zm00001d049958, Zm00001d027359, Zm00001d048502 and Zm00001d052138, were identified as being related to meristem development, which corroborated their roles in the superior additive genetic effects on ear length in T121 line. Non-additive expression patterns were used to identify candidate genes related to ear-length heterosis. A non-additively expressed gene (Zm00001d050649) was associated with the timing of meristematic phase transition and was determined to be the homolog of tomato SELF PRUNING, which assists SINGLE FLOWER TRUSS in driving yield-related heterosis, indicating that Zm00001d050649 is a potential contributor to drive heterotic effect on ear length. CONCLUSION: Our results suggest that inbred parents provide genetic and heterotic effects on the ear lengths of their corresponding F1 hybrids through two independent pathways. These findings provide comprehensive insights into the transcriptional regulation of ear length and improve the understanding of ear-length heterosis in maize.
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Vigor Híbrido , Fitomejoramiento , Zea mays/crecimiento & desarrollo , Zea mays/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Hibridación Genética , Endogamia , Reacción en Cadena en Tiempo Real de la Polimerasa , TranscriptomaRESUMEN
Recurrent event data frequently arise in longitudinal studies and observations on recurrent events could be terminated by a major failure event such as death. In many situations, there exist a large fraction of subjects without any recurrent events of interest. Among these subjects, some are unsusceptible to recurrent events, while others are susceptible but have no recurrent events being observed due to censoring. In this article, we propose a zero-inflated generalized joint frailty model and a sieve maximum likelihood approach to analyze zero-inflated recurrent events with a terminal event. The model provides a considerable flexibility in formulating the effects of covariates on both recurrent events and the terminal event by specifying various transformation functions. In addition, Bernstein polynomials are employed to approximate the unknown cumulative baseline hazard (intensity) function. The estimation procedure can be easily implemented and is computationally fast. Extensive simulation studies are conducted and demonstrate that our proposed method works well for practical situations. Finally, we apply the method to analyze myocardial infarction recurrences in the presence of death in a clinical trial with cardiovascular outcomes.
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Modelos Estadísticos , Simulación por Computador , Humanos , Funciones de Verosimilitud , Estudios Longitudinales , RecurrenciaRESUMEN
Hypoglycemia is a major safety concern for diabetic patients. Hypoglycemic events can be modeled based on time to recurrent events or count data. In this article, we evaluated a gamma frailty model with variance estimated by the inverse of observed Fisher information matrix, a gamma frailty model with the sandwich variance estimator, and a piecewise negative binomial regression model. Simulations showed that the sandwich variance estimator performed better when the frailty model is mis-specified, and the piecewise negative binomial regression sometimes fails to converge. All three methods were applied to a dataset from a clinical trial evaluating insulin treatments.
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Hipoglucemia , Humanos , Hipoglucemia/epidemiología , Modelos Estadísticos , RecurrenciaRESUMEN
This study was conducted for the metagenomic analysis of stool samples from CRC affected individuals to identify biomarkers for CRC in Hainan, the only tropical island province of China. The gut microbiota of CRC patients differed significantly from that of healthy and reference database cohorts based on Aitchison distance and Bray-Cutis distance but there was no significant difference in alpha diversity. Furthermore, at the species level, 68 species were significantly altered including 37 CRC-enriched, such as, Fusobacterium nucleatum, Parvimonas micra, Gemella morbillorum, Citrobacter portucalensis, Alloprevotella sp., Shigella sonnei, Coriobacteriaceae bacterium, etc. Sixty-seven different metabolic pathways were acquired, and pathways involved in the synthesis of many amino acids were significantly declined. Besides, 2 identified antibiotic resistance genes performed well (area under the receive-operation curve AUC = 0.833, 95% CI 58.51-100%) compared with virulence factor genes. The results of the present study provide region-specific bacterial and functional biomarkers of gut microbiota for CRC patients in Hainan. Microbiota is considered as a non-invasive biomarker for the detection of CRC. Gut microbiota of different geographic regions should be further studied to expand the understanding of markers, especially for the China cohort due to diverse nationalities and lifestyles.
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Neoplasias Colorrectales , Biomarcadores , China , Citrobacter , Firmicutes , Gemella , HumanosRESUMEN
Cyclin-dependent kinase 5 (Cdk5) has been shown to play a critical role in brain development, learning, memory and neural processing in general. Cdk5 is widely distributed in many neuron types in the central nervous system, while its cell-specific role is largely unknown. Our previous study showed that Cdk5 inhibition restored ocular dominance (OD) plasticity in adulthood. In this study, we specifically knocked down Cdk5 in different types of neurons in the visual cortex and examined OD plasticity by optical imaging of intrinsic signals. Downregulation of Cdk5 in parvalbumin-expressing (PV) inhibitory neurons, but not other neurons, reactivated adult mouse visual cortical plasticity. Cdk5 knockdown in PV neurons reduced the evoked firing rate, which was accompanied by an increment in the threshold current for the generation of a single action potential (AP) and hyperpolarization of the resting membrane potential. Moreover, chemogenetic activation of PV neurons in the visual cortex can attenuate the restoration of OD plasticity by Cdk5 inhibition. Taken together, our results suggest that Cdk5 in PV interneurons may play a role in modulating the excitation and inhibition balance to control the plasticity of the visual cortex.
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Quinasa 5 Dependiente de la Ciclina/fisiología , Predominio Ocular , Plasticidad Neuronal , Neuronas/metabolismo , Corteza Visual/enzimología , Animales , Quinasa 5 Dependiente de la Ciclina/genética , Quinasa 5 Dependiente de la Ciclina/metabolismo , Técnicas de Silenciamiento del Gen , Masculino , Ratones , Neuronas/fisiología , Corteza Visual/fisiologíaRESUMEN
BACKGROUND: Numerous studies have reported the health-promoting effects of exopolysaccharides (EPSs) in in vitro models; however, a functional evaluation of EPSs will provide additional knowledge of EPS-microbe interactions by in vivo intestinal microbial model. In the present study, high-throughput amplicon sequencing, short-chain fatty acid (SCFAs) and intestinal inflammation evaluation were performed to explore the potential benefits of exopolysaccharides (EPSs) and EPS-producing Lactobacillus (HNUB20 group) using the healthy zebrafish (Danio rerio) model. RESULTS: The results based on microbial taxonomic analysis revealed that the abundance of four genera, Ochrobactrum, Sediminibacterium, Sphingomonas and Sphingobium, were increased in the control group in comparison to HNUB20 group. Pelomonas spp. levels were significantly higher and that of the genera Lactobacillus and Brachybacterium were significantly decreased in EPS group compared with control group. PICRUSt based functional prediction of gut microbiota metabolic pathways indicated that significantly lower abundance was found for transcription, and membrane transport, whereas folding, sorting and degradation and energy metabolism had significantly higher abundance after HNUB20 treatment. Two metabolic pathways, including metabolism and endocrine functions, were more abundant in the EPS group than control group. Similar to the HNUB20 group, transcription was also decreased in the EPS group compared with the control group. However, SCFAs and immune indexes indicated EPS and HNUB20 performed limited efficacy in the healthy zebrafish. CONCLUSIONS: The present intestinal microbial model-based study indicated that EPSs and high-yield EPS-producing Lactobacillus can shake the structure of intestinal microbiota, but cannot change SCFAs presence and intestinal inflammation.
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Microbioma Gastrointestinal/fisiología , Intestinos/microbiología , Lactobacillus/fisiología , Polisacáridos Bacterianos/farmacología , Pez Cebra/microbiología , Actinobacteria/fisiología , Animales , Bacteroidetes/fisiología , Comamonadaceae/fisiología , Ácidos Grasos Volátiles/metabolismo , Femenino , Masculino , Redes y Vías Metabólicas/genética , Ochrobactrum/fisiología , Polisacáridos Bacterianos/biosíntesis , Sphingomonadaceae/fisiología , Sphingomonas/fisiología , Transcripción GenéticaRESUMEN
Pinellia ternata belongs to the Araceae family and is a medicinal herb. The tuber is the medicinal organ with antitussive, antiemetic and anti-tumor activities. It is easy to encounter high temperature environment during the growth periods, leading to decrease of tuber production. At present, the mechanism of response to high temperature stress in P. ternata is still unknown. DNA methylation plays a vital role in plant protection against adversity stress as a way of epigenetic regulation. In this study, P. ternata was used as material for treatment of high temperature stress at 0 h, 6 h and 80 h, and methylation sensitive amplification polymorphism(MSAP) analysis was conducted on the changes of DNA methylation in its genome. The results showed that 20 pairs of MSAP primers were selected from 100 MSAP primers with multiple clear and uniform bands, and 353, 355 and 342 loci were amplified from materials of P. ternata treated in the high temperature stress 0 h, 6 h and 80 h, respectively. Cytosine methylation levels of CCGG context in the above materials were characterized as 60.91%, 44.79% and 44.74%, respectively. And the full methylation ratios were 16.71%, 22.25% and 29.24, respectively. It demonstrated that high temperature stress significantly induced the down-regulation of DNA methylation level and up-regulation of the full methylation rate in P. ternata genome. This study provides a preliminary theoretical reference for analyzing the mechanism of P. ternata responding to high temperature stress from the epigenetic perspective.
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Metilación de ADN , Epigénesis Genética , Calor , Pinellia/genética , Plantas Medicinales/genéticaRESUMEN
Fast detection of Pb2+ pollution has become an important issue in the environment field and food industry. In this work, electrospun nanofibrous cellulose acetate/curcumin membranes (ENCACMs) and pure cellulose acetate (CA) membranes were fabricated by the electrospinning technique. Then the fast detection of heavy metals by these membranes was observed by naked eyes and digital camera. Fabricated ENCACMs showed obvious selectivity to the Pb2+ at pH 9. Pb2+ detection sensitivity of ENCACMs with a thickness of 0.2 mm was 1 mM (limit of detection) at pH 9. The sensitivity depended on the pH of solution and membrane thickness. However, it was not incubation time dependent. This work provides a simple, cheap, and fast method for detecting Pb2+. Moreover, this method is environmentally friendly to the detection solution and is simply post-treated after the detection process.
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BACKGROUND: Using next-generation sequencing technology to measure gene expression, an empirically intriguing question concerns the identification of differentially expressed genes across treatment groups. Existing methods aim to identify genes whose mean expressions differ among treatment groups by assuming equal dispersion across all groups. For syndromes, however, various combinations of gene expression alterations can result in the same disease, leading to greater heteroscedasticity in the biological replicates in the disease group compared to the normal group. Traditional methods that only consider changes in the mean will fail to fully analyze gene expression in such a scenario. In addition, sequencing technology is relatively expensive; most labs can only afford a few replicates per treatment group, which poses further challenges to reliably estimating the mean and dispersion under each treatment condition. RESULTS: We designed an empirical Bayes method and a pooled permutation test to simultaneously consider the change in mean and dispersion across treatment groups. We further computed confidence intervals based on Bayes estimates to identify differentially expressed genes that are unique to each disease sample as well as those that are common across all disease samples. We illustrated our method by applying it to gene expression data from a large offspring syndrome experiment, which motivated this study. We compared our method to competing approaches through simulation studies that mimicked the real datasets to demonstrate the effectiveness of our proposed method. CONCLUSIONS: We will show that, compared to popular methods that only aim to find the difference in the mean, our method can capture greater variation in the disease group to effectively identify differentially expressed genes for syndromes.
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Teorema de Bayes , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica/genética , Humanos , SíndromeRESUMEN
Objective: Nonribosomal peptide synthetase (NRPS) plays an important role in plant-pathogenic fungi interaction. In this study, we analyzed the role of VmNRPS12 during Valsa mali (V. mali) infection and pathogenecity, which may shed new insights into the pathogenesis of V. mali. Methods: Based on the genome of V. mali, we obtained one NPRS, designated as VmNRPS12. The expression profile of VmNRPS12 was analyzed by qRT-PCR. Through Double-joint PCR and PEG-mediated protoplast transformation, VmNRPS12-knockout mutants were generated. PCR and Southern blot hybridization were applied to verify the positive mutant. Then genetic complementation was performed by transforming mutant protoplast with VmNRPS12 original gene. Finally, vegetative growth, conidiation and pathogenicity were examined. Results: qRT-PCR analyses showed that VmNRPS12 was upregulated during the early infection stages of V. mali, and expressed remarkably at 48 hours post inoculation (138.6-fold). Compared with the wild type 03-8, VmNRPS12-knockout mutant showed no obvious change in vegetative growth and conidiation on PDA medium. Notably, the VmNRPS12-knockout mutant exhibited significantly reduced virulence on apple twigs. Furthermore, complementation of VmNRPS12 restored the pathogenecity of the VmNRPS12-knockout mutant approximately to the wild type 03-8. Conclusion: VmNRPS12 contributes positively to the pathogenicity of V. mali.
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Ascomicetos/enzimología , Proteínas Fúngicas/metabolismo , Malus/microbiología , Péptido Sintasas/metabolismo , Enfermedades de las Plantas/microbiología , Ascomicetos/genética , Ascomicetos/patogenicidad , Proteínas Fúngicas/genética , Péptido Sintasas/genética , VirulenciaRESUMEN
BACKGROUND: FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated gene in acute myeloid leukemia. As a receptor tyrosine kinase (RTK), FLT3 plays a role in the proliferation and differentiation of hematopoietic stem cells. As the most frequent molecular alteration in AML, FLT3 has drawn the attention of many researchers, and a lot of small molecule inhibitors targeting FLT3 have been intensively investigated as potential drugs for AML therapy. METHODS: In this paper, PubMed and SciFinder® were used as a tool; the publications about "FLT3 inhibitor" and "Acute myeloid leukemia" were surveyed from 2014 to the present with an exclusion of those published as patents. RESULTS: In this study, the structural characterization and biological activities of representative FLT3 inhibitors were summarized. The major challenges and future directions for further research are discussed. CONCLUSION: Recently, numerous FLT3 inhibitors have been discovered and employed in FLT3-mutated AML treatment. In order to overcome the drug resistance caused by FLT3 mutations, screening multitargets FLT3 inhibitors has become the main research direction. In addition, the emergence of irreversible FLT3 inhibitors also provides new ideas for discovering new FLT3 inhibitors.
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Antineoplásicos , Leucemia Mieloide Aguda , Inhibidores de Proteínas Quinasas , Tirosina Quinasa 3 Similar a fms , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Tirosina Quinasa 3 Similar a fms/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Desarrollo de MedicamentosRESUMEN
Patients with post-traumatic stress disorder (PTSD) exhibit sex differences in symptomology, with women more likely to report higher rates of intrusive and avoidance symptoms than men, underscoring the need for sex-informed approaches to research and treatment. Our study delved into the sex-specific aspects of stress-induced visual impairments using the single prolonged stress (SPS) model, a partially validated rodent model for PTSD. Male SPS mice exhibit heightened optimal spatial frequency (SF) of primary visual cortex (V1) neurons, while female counterparts exhibit decreased optimal temporal frequency (TF) of V1 neurons. This phenomenon persisted until the 29th day after SPS modeling, and it may be the physiological basis for the observed increase in visual acuity in male SPS mice in visual water task. Furthermore, our study found that corticotropin-releasing factor receptor 1 regulated optimal TF and optimal SF of V1 in mice, but did not exhibit sex differences. These findings indicated that severe stress induces sex-specific effects on visual function.
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Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Receptores de Hormona Liberadora de Corticotropina , Caracteres Sexuales , Estrés Psicológico , Animales , Masculino , Femenino , Estrés Psicológico/fisiopatología , Estrés Psicológico/psicología , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Ratones , Neuronas/fisiología , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/psicología , Corteza Visual Primaria/fisiología , Agudeza Visual/fisiología , Corteza VisualRESUMEN
The occurrence and progression of tumors are often accompanied by disruptions in the gut microbiota. Inversely, the impact of the gut microbiota on the initiation and progression of cancer is becoming increasingly evident, influencing the tumor microenvironment (TME) for both local and distant tumors. Moreover, it is even suggested to play a significant role in the process of tumor immunotherapy, contributing to high specificity in therapeutic outcomes and long-term effectiveness across various cancer types. Probiotics, with their generally positive influence on the gut microbiota, may serve as effective agents in synergizing cancer immunotherapy. They play a crucial role in activating the immune system to inhibit tumor growth. In summary, this comprehensive review aims to provide valuable insights into the dynamic interactions between probiotics, gut microbiota, and cancer. Furthermore, we highlight recent advances and mechanisms in using probiotics to improve the effectiveness of cancer immunotherapy. By understanding these complex relationships, we may unlock innovative approaches for cancer diagnosis and treatment while optimizing the effects of immunotherapy.
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Microbioma Gastrointestinal , Inmunoterapia , Neoplasias , Probióticos , Microambiente Tumoral , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Probióticos/farmacología , Humanos , Inmunoterapia/métodos , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/microbiología , Microambiente Tumoral/inmunología , AnimalesRESUMEN
The protein phosphatase PP2C plays an important role in plant responses to stress. Therefore, the identification of maize PP2C genes that respond to drought stress is particularly important for the improvement and creation of new drought-resistant assortments of maize. In this study, we identified 102 ZmPP2C genes in maize at the genome-wide level. We analyzed the physicochemical properties of 102 ZmPP2Cs and constructed a phylogenetic tree with Arabidopsis. By analyzing the gene structure, conserved protein motifs, and synteny, the ZmPP2Cs were found to be strongly conserved during evolution. Sixteen core genes involved in drought stress and rewatering were screened using gene co-expression network mapping and expression profiling. The qRT-PCR results showed 16 genes were induced by abscisic acid (ABA), drought, and NaCl treatments. Notably, ZmPP2C15 exhibited a substantial expression difference. Through genetic transformation, we overexpressed ZmPP2C15 and generated the CRISPR/Cas9 knockout maize mutant zmpp2c15. Overexpressing ZmPP2C15 in Arabidopsis under drought stress enhanced growth and survival compared with WT plants. The leaves exhibited heightened superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), and catalase (CAT) activities, elevated proline (Pro) content, and reduced malondialdehyde (MDA) content. Conversely, zmpp2c15 mutant plants displayed severe leaf dryness, curling, and wilting under drought stress. Their leaf activities of SOD, POD, APX, and CAT were lower than those in B104, while MDA was higher. This suggests that ZmPP2C15 positively regulates drought tolerance in maize by affecting the antioxidant enzyme activity and osmoregulatory substance content. Subcellular localization revealed that ZmPP2C15 was localized in the nucleus and cytoplasm. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) experiments demonstrated ZmPP2C15's interaction with ZmWIN1, ZmADT2, ZmsodC, Zmcab, and ZmLHC2. These findings establish a foundation for understanding maize PP2C gene functions, offering genetic resources and insights for molecular design breeding for drought tolerance.