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Drought stress limits crop yield, but the molecular modulators and their mechanisms underlying the trade-off between drought resistance and crop growth and development remain elusive. Here, a grain width and weight2 (GW2)-like really interesting new gene finger E3 ligase, TaGW2, was identified as a pivotal regulator of both kernel development and drought responses in wheat (Triticum aestivum). TaGW2 overexpression enhances drought resistance but leads to yield drag under full irrigation conditions. In contrast, TaGW2 knockdown or knockout attenuates drought resistance but remarkably increases kernel size and weight. Furthermore, TaGW2 directly interacts with and ubiquitinates the type-B Arabidopsis response regulator TaARR12, promoting its degradation via the 26S proteasome. Analysis of TaARR12 overexpression and knockdown lines indicated that TaARR12 represses the drought response but does not influence grain yield in wheat. Further DNA affinity purification sequencing combined with transcriptome analysis revealed that TaARR12 downregulates stress-responsive genes, especially group-A basic leucine zipper (bZIP) genes, resulting in impaired drought resistance. Notably, TaARR12 knockdown in the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9)-mediated tagw2 knockout mutant leads to significantly higher drought resistance and grain yield compared to wild-type plants. Collectively, these findings show that the TaGW2-TaARR12 regulatory module is essential for drought responses, providing a strategy for improving stress resistance in high-yield wheat varieties.
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Sementes , Triticum , Sementes/genética , Triticum/metabolismo , Resistência à Seca , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Grão Comestível/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Secas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Allotetraploid cotton (Gossypium) species represents a model system for the study of plant polyploidy, molecular evolution, and domestication. Here, chromosome-scale genome sequences were obtained and assembled for two recently described wild species of tetraploid cotton, Gossypium ekmanianum [(AD)6, Ge] and Gossypium stephensii [(AD)7, Gs], and one early form of domesticated Gossypium hirsutum, race punctatum [(AD)1, Ghp]. Based on phylogenomic analysis, we provide a dated whole-genome level perspective for the evolution of the tetraploid Gossypium clade and resolved the evolutionary relationships of Gs, Ge, and domesticated G. hirsutum. We describe genomic structural variation that arose during Gossypium evolution and describe its correlates-including phenotypic differentiation, genetic isolation, and genetic convergence-that contributed to cotton biodiversity and cotton domestication. Presence/absence variation is prominent in causing cotton genomic structural variations. A presence/absence variation-derived gene encoding a phosphopeptide-binding protein is implicated in increasing fiber length during cotton domestication. The relatively unimproved Ghp offers the potential for gene discovery related to adaptation to environmental challenges. Expanded gene families enoyl-CoA δ isomerase 3 and RAP2-7 may have contributed to abiotic stress tolerance, possibly by targeting plant hormone-associated biochemical pathways. Our results generate a genomic context for a better understanding of cotton evolution and for agriculture.
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Evolução Molecular , Genoma de Planta , Gossypium , Fibra de Algodão , Variação Genética/genética , Genoma de Planta/genética , Gossypium/classificação , Gossypium/genética , Isomerases/genética , Isomerases/metabolismo , TetraploidiaRESUMO
BACKGROUND: Epidermal patterning factor / -like (EPF/EPFL) gene family encodes a class of cysteine-rich secretory peptides, which are widelyfound in terrestrial plants.Multiple studies has indicated that EPF/EPFLs might play significant roles in coordinating plant development and growth, especially as the morphogenesis processes of stoma, awn, stamen, and fruit skin. However, few research on EPF/EPFL gene family was reported in Gossypium. RESULTS: We separately identified 20 G. raimondii, 24 G. arboreum, 44 G. hirsutum, and 44 G. barbadense EPF/EPFL genes in the 4 representative cotton species, which were divided into four clades together with 11 Arabidopsis thaliana, 13 Oryza sativa, and 17 Selaginella moellendorffii ones based on their evolutionary relationships. The similar gene structure and common motifs indicated the high conservation among the EPF/EPFL members, while the uneven distribution in chromosomes implied the variability during the long-term evolutionary process. Hundreds of collinearity relationships were identified from the pairwise comparisons of intraspecifc and interspecific genomes, which illustrated gene duplication might contribute to the expansion of cotton EPF/EPFL gene family. A total of 15 kinds of cis-regulatory elements were predicted in the promoter regions, and divided into three major categories relevant to the biological processes of development and growth, plant hormone response, and abiotic stress response. Having performing the expression pattern analyses with the basic of the published RNA-seq data, we found most of GhEPF/EPFL and GbEPF/EPFL genes presented the relatively low expression levels among the 9 tissues or organs, while showed more dramatically different responses to high/low temperature and salt or drought stresses. Combined with transcriptome data of developing ovules and fibers and quantitative Real-time PCR results (qRT-PCR) of 15 highly expressed GhEPF/EPFL genes, it could be deduced that the cotton EPF/EPFL genes were closely related with fiber development. Additionally, the networks of protein-protein interacting among EPF/EPFLs concentrated on the cores of GhEPF1 and GhEPF7, and thosefunctional enrichment analyses indicated that most of EPF/EPFLs participate in the GO (Gene Ontology) terms of stomatal development and plant epidermis development, and the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of DNA or base excision repair. CONCLUSION: Totally, 132 EPF/EPFL genes were identified for the first time in cotton, whose bioinformatic analyses of cis-regulatory elements and expression patterns combined with qRT-PCR experiments to prove the potential functions in the biological processes of plant growth and responding to abiotic stresses, specifically in the fiber development. These results not only provide comprehensive and valuable information for cotton EPF/EPFL gene family, but also lay solid foundation for screening candidate EPF/EPFL genes in further cotton breeding.
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Gossypium , Família Multigênica , Proteínas de Plantas , Gossypium/genética , Gossypium/metabolismo , Gossypium/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Genes de Plantas , Estudo de Associação Genômica Ampla , Perfilação da Expressão Gênica , Mapas de Interação de ProteínasRESUMO
Methyltransferase like 3 (METTL3), a primary N6-methyladenosine (m6A) methyltransferase, has been implicated in various biological and pathological processes including immune responses. However, the functions and mechanisms of METTL3 in pathogenic T helper (Th)17 cells are poorly understood. Here we found significantly decreased METTL3 expression along with reduced m6A levels in eyeballs and T cells of experimental autoimmune uveitis (EAU). Overexpression of METTL3 ameliorated the development of EAU and suppressed pathogenic Th17 cell responses in vivo and in vitro. Mechanistically, METTL3 promoted the expression of absent, small, or homeotic-like 1 (ASH1L) via enhancing its stability in a YT521-B homology domain containing 2 (YTHDC2)-dependent manner, which further decreased the expression of IL-17 and IL-23 receptor (IL-23R), resulting in reduced pathogenic Th17 responses. Together, our data reveal a pivotal role of METTL3 in regulating pathogenic Th17 responses, which may contribute to human uveitis therapy.
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Proteínas de Ligação a DNA , Histona-Lisina N-Metiltransferase , Metiltransferases , Células Th17 , Uveíte , Proteínas de Ligação a DNA/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , RNA Mensageiro/genética , Uveíte/genética , Uveíte/metabolismo , Animais , Doenças Autoimunes , Modelos Animais de DoençasRESUMO
Pathogenic Th17 cells are critical drivers of multiple autoimmune diseases, including uveitis and its animal model, experimental autoimmune uveitis (EAU). However, how innate immune signals modulate pathogenic Th17 responses remains largely unknown. Here, we showed that miR-338-3p endowed dendritic cells (DCs) with an increased ability to activate interphotoreceptor retinoid-binding protein (IRBP)1-20 -specific Th17 cells by promoting the production of IL-6, IL-1ß, and IL-23. In vivo administration of LV-miR-338-infected DCs promoted pathogenic Th17 responses and exacerbated EAU development. Mechanistically, dual-specificity phosphatase 16 (Dusp16) was a molecular target of miR-338-3p. miR-338-3p repressed Dusp16 and therefore strengthened the mitogen-activated protein kinase (MAPK) p38 signaling, resulting in increased production of Th17-polarizing cytokines and subsequent pathogenic Th17 responses. In addition, methyltransferase like 3 (Mettl3), a key m6A methyltransferase, mediated the upregulation of miR-338-3p in activated DCs. Together, our findings identify a vital role for Mettl3/miR-338-3p/Dusp16/p38 signaling in DCs-driven pathogenic Th17 responses and suggest a potential therapeutic avenue for uveitis and other Th17 cell-related autoimmune disorders.
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Doenças Autoimunes , MicroRNAs , Uveíte , Animais , Células Th17 , Doenças Autoimunes/genética , Metiltransferases , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Uveíte/genética , Células Dendríticas , MicroRNAs/genéticaRESUMO
The natural aging process is accompanied by changes in exosomes, gut microbiota, and metabolites. This study aimed to reveal the anti-aging effect and mechanisms of fecal microbiota transplantation (FMT) from young donors on the natural aging process in mice by analyzing exosomes, gut microbiota, and metabolomics. Aging-relevant telomeric length, oxidative stress indexes in brain tissue, and serum cytokine levels were measured. Flow analysis of T-regulatory (Treg), CD4+, and CD8+ cells was performed, and the expression levels of aging-related proteins were quantified. High-throughput sequencing technology was used to identify differentially expressed serum exosomal miRNAs. Fecal microbiota was tested by 16â¯S rDNA sequencing. Changes in fecal metabolites were analyzed by UPLC-Q-TOF/MS. The results indicated that the expression of mmu-miR-7010-5p, mmu-miR-376b-5p, mmu-miR-135a-5p, and mmu-miR-3100-5p by serum exosomes was down-regulated and the abundance of opportunistic bacteria (Turicibacter, Allobaculum, Morganella.) was decreased, whereas the levels of protective bacteria (Akkermansia, Muribaculaceae, Helicobacter.) were increased after FMT. Metabolic analysis identified 25 potential biomarkers. Correlation analysis between the gut microbiota and metabolites suggested that the relative abundance of protective bacteria was positively correlated with the levels of spermidine and S-adenosylmethionine. The study indicated that FMT corrected brain injury due to aging via lipid metabolism, the metabolism of cofactors and vitamins, and amino acid metabolism.
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Envelhecimento , Encéfalo , Exossomos , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Metabolômica , Camundongos Endogâmicos C57BL , MicroRNAs , Animais , Encéfalo/metabolismo , MicroRNAs/metabolismo , Exossomos/metabolismo , Masculino , Camundongos , Estresse Oxidativo , Citocinas/metabolismo , Citocinas/sangueRESUMO
BACKGROUND AND AIM: Limited data are available regarding pre-liver transplantation (LT) bacteremia in adults with end-stage liver disease. In this study, we investigated the risk factors independently associated with pre-LT bacteremia and their effects on clinical outcomes of LT. METHODS: This retrospective study performed between 2010 and 2021 included 1287 LT recipients. The study population was categorized into patients with pre-LT bacteremia and those without pre-LT infection. Pre-LT bacteremia was defined as bacteremia detected within 90 days before LT. RESULTS: Among 1287 LT recipients, 92 (7.1%) developed pre-LT bacteremia. The mean interval between bacteremia and LT was 28.3 ± 19.5 days. Of these 92 patients, seven (7.6%) patients died after LT. Of the 99 microorganisms isolated in this study, gram-negative bacteria were the most common microbes (72.7%). Bacteremia was mainly attributed to spontaneous bacterial peritonitis. The most common pathogen isolated was Escherichia coli (25.2%), followed by Klebsiella pneumoniae (18.2%), and Staphylococcus aureus (15.1%). Multivariate analysis showed that massive ascites (adjusted odds ratio [OR] 1.67, 95% confidence Interval [CI] 1.048-2.687) and a prolonged international normalized ratio for prothrombin time (adjusted OR 1.13, 95% CI 1.074-1.257) were independent risk factors for pre-LT bacteremia in patients with end-stage liver disease. Intensive care unit and in-hospital stay were significantly longer, and in-hospital mortality was significantly higher among LT recipients with pre-LT bacteremia than among those without pre-LT infection. CONCLUSIONS: This study highlights predictors of pre-LT bacteremia in patients with end-stage liver disease. Pre-LT bacteremia increases the post-transplantation mortality risk.
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Bacteriemia , Doença Hepática Terminal , Transplante de Fígado , Adulto , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Doença Hepática Terminal/complicações , Doença Hepática Terminal/cirurgia , Fatores de Risco , Bacteriemia/epidemiologiaRESUMO
Oxygen vacancies and heteroatom doping play important role in oxygen reduction activity of metal oxides. Developing efficient modification method is one of the key issues in catalysts research. Room temperature plasma treatment, with the advantages of mild working conditions, no emissions and high efficiency, is a new catalyst modification method developed in recent years. In this work, hydrothermal synthesizedα-MnO2nanorods are treated in NH3plasma at room temperature. In the reducing atmosphere, oxygen vacancies and N doping are achieved simultaneously on the surface. The NH3plasma etched MnO2demonstrate a significant enhanced oxygen reduction activity with half-wave potential of 0.84 V, limiting current density of 6.32 mA cm-2and transferred electrons number of 3.9. The Mg-air battery with N-MnO2display a maximum power density of 76.3 mW cm-2as well as stable discharge performance. This work provides new ideas for preparing efficient and cost-effective method to boost the catalysts activity.
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Mild traumatic brain injury (mTBI) disrupts the integrity of white matter microstructure, which affects brain functional connectivity supporting cognitive function. Although the relationship between structural and functional connectivity (SC and FC), here called SC-FC coupling, has been studied on global level in brain disorders, the long-term disruption of SC-FC coupling in mTBI at regional scale was still unclear. The current study investigated the alteration pattern of regional SC-FC coupling in 104 acute mTBI patients (41 with 6-12 months of follow-up) and 56 healthy controls (HCs). SC and FC networks were constructed to measure regional, intra-network, and inter-network SC-FC coupling. Compared with HCs, acute mTBI exhibited altered SC-FC coupling of the sensorimotor network (SMN). The coupling laterality indicators of the SMN can identify mTBI from controls. The persistent SC-FC decoupling of the SMN and the additional decoupling of the default mode network (DMN) were observed in chronic mTBI. Crucially, decoupling of the SMN and DMN predicted better cognitive outcomes. The findings revealed the SC-FC coupling alternations exhibited hierarchical trend originating from the sensorimotor cortex to high-order cognitive regions with the progression of mTBI. The regional and hierarchical SC-FC coupling may be a prognostic biomarker to provide insights into the pathophysiology mechanism of mTBI.
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Concussão Encefálica , Disfunção Cognitiva , Humanos , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico por imagem , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento EncefálicoRESUMO
Traumatic brain injury (TBI) disrupt the coordinated activity of triple-network and produce impairments across several cognitive domains. The triple-network model posits a key role of the salience network (SN) that regulates interactions with the central executive network (CEN) and default mode network (DMN). However, the aberrant dynamic interactions among triple-network and associations with neurobehavioral symptoms in mild TBI was still unclear. In present study, we used brain network interaction index (NII) and dynamic functional connectivity to examine the time-varying cross-network interactions among the triple-network in 109 acute patients, 41 chronic patients, and 65 healthy controls. Dynamic cross-network interactions were significantly increased and more variable in mild TBI compared to controls. Crucially, mild TBI exhibited an increased NII as enhanced integrations between the SN and CEN while reduced coupling of the SN with DMN. The increased NII also implied much severer and multiple domains of cognitive impairments at both acute and chronic mild TBI. Abnormities in time-varying engagement of triple-network is a clinically relevant neurobiological signature of psychopathology in mild TBI. The findings provided align with and advance an emerging perspective on the importance of aberrant brain dynamics associated with highly disparate cognitive and behavioral outcomes in trauma.
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Concussão Encefálica , Disfunção Cognitiva , Humanos , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico por imagem , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Rede Nervosa , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologiaRESUMO
BACKGROUND: The development of cotton fiber is regulated by the orchestrated binding of regulatory proteins to cis-regulatory elements associated with developmental genes. The cis-trans regulatory dynamics occurred throughout the course of cotton fiber development are elusive. Here we generated genome-wide high-resolution DNase I hypersensitive sites (DHSs) maps to understand the regulatory mechanisms of cotton ovule and fiber development. RESULTS: We generated DNase I hypersensitive site (DHS) profiles from cotton ovules at 0 and 3 days post anthesis (DPA) and fibers at 8, 12, 15, and 18 DPA. We obtained a total of 1185 million reads and identified a total of 199,351 DHSs through ~ 30% unique mapping reads. It should be noted that more than half of DNase-seq reads mapped multiple genome locations and were not analyzed in order to achieve a high specificity of peak profile and to avoid bias from repetitive genomic regions. Distinct chromatin accessibilities were observed in the ovules (0 and 3 DPA) compared to the fiber elongation stages (8, 12, 15, and 18 DPA). Besides, the chromatin accessibility during ovules was particularly elevated in genomic regions enriched with transposable elements (TEs) and genes in TE-enriched regions were involved in ovule cell division. We analyzed cis-regulatory modules and revealed the influence of hormones on fiber development from the regulatory divergence of transcription factor (TF) motifs. Finally, we constructed a reliable regulatory network of TFs related to ovule and fiber development based on chromatin accessibility and gene co-expression network. From this network, we discovered a novel TF, WRKY46, which may shape fiber development by regulating the lignin content. CONCLUSIONS: Our results not only reveal the contribution of TEs in fiber development, but also predict and validate the TFs related to fiber development, which will benefit the research of cotton fiber molecular breeding.
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Cromatina , Fatores de Transcrição , Cromatina/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Óvulo Vegetal/genética , Óvulo Vegetal/metabolismo , Redes Reguladoras de Genes , Desoxirribonuclease I/genéticaRESUMO
Monitoring the level of biothiols in organisms would be beneficial for health inspections. Recently, 3-(2'-nitro vinyl)-4-phenylselenyl coumarin as a fluorescent probe for distinguishing the detection of the small-molecule biothiols cysteine/homocysteine (Cys/Hcy) and glutathione (GSH) was developed. By introducing 4-phenyselenium as the active site, the probe CouSeNO2/CouSNO2 was capable of detecting Cys/Hcy and GSH in dual fluorescence channels. Theoretical insights into the fluorescence sensing mechanism of the probe were provided in this work. The details of the electron excitation process in the probe and sensing products under optical excitation and the fluorescent character were analyzed using the quantum mechanical method. All these theoretical results would provide insight and pave the way for the molecular design of fluorescent probes for the detection of biothiols.
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Cisteína , Corantes Fluorescentes , Corantes Fluorescentes/química , Cisteína/química , Glutationa/química , Cumarínicos/química , Espectrometria de Fluorescência/métodos , HomocisteínaRESUMO
Piperlongumine(PL), a natural alkaloid extracted from Piperis Longi Fructus, has attracted much attention in recent years because of its strong anti-tumor activity, little toxicity to normal cells, and excellent sensitizing effect combined with chemotherapy and radiotherapy, which endow PL with unique advantages as an anti-tumor drug. However, similar to other alkaloids, PL has low water solubility and poor bioavailability. To improve the application of PL in the clinical treatment of tumors, researchers have constructed various nano-drug delivery systems to increase the efficiency of PL delivery. This paper reviewed the physicochemical properties, anti-tumor mechanism, combined therapies, and nano-drug delivery systems of PL in recent years. The review aimed to provide a reference for further research on the anti-tumor effect and nano-drug delivery system of PL. Moreover, this review is expected to provide a reference for the development and application of PL in the anti-tumor therapies.
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Dioxolanos , Neoplasias , Dioxolanos/química , Humanos , Animais , Neoplasias/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/administração & dosagem , Sistemas de Liberação de Fármacos por Nanopartículas/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , PiperidonasRESUMO
BACKGROUND: Ophiopogon japonicus, mainly planted in Sichuan (CMD) and Zhejiang (ZMD) province in China, has a lengthy cultivation history. During the long period of domestication, the genetic diversity of cultivated O. japonicus has substantially declined, which will affect the population continuity and evolutionary potential of this species. Therefore, it is necessary to clarify the phylogeography of cultivated O. japonicus to establish a theoretical basis for the utilization and conservation of the genetic resources of O. japonicus. RESULT: The genetic diversity and population structure of 266 O. japonicus individual plants from 23 sampling sites were analyzed based on 4 chloroplast DNA sequences (atpB-rbcL, rpl16, psbA-trnH and rpl20-5'rps12) to identify the effects of domestication on genetic diversity of cultivars and determine their geographic origins. The results showed that cultivated O. japonicus and wild O. japonicus had 4 and 15 haplotypes respectively. The genetic diversity of two cultivars (Hd = 0.35700, π = 0.06667) was much lower than that of the wild populations (Hd = 0.76200, π = 0.20378), and the level of genetic diversity in CMD (Hd = 0.01900, π = 0.00125) was lower than that in ZMD (Hd = 0.06900, π = 0.01096). There was significant difference in genetic differentiation between the cultivated and the wild (FST = 0.82044), especially between the two cultivars (FST = 0.98254). This species showed a pronounced phylogeographical structure (NST > GST, P < 0.05). The phylogenetic tree showed that the genetic difference between CMD and ZMD was not enough to distinguish the cultivars between the two producing areas by using O. amblyphyllus Wang et Dai as an outgroup. In addition, both CMD and ZMD have a closer relationship with wild populations in Sichuan than that in Zhejiang. The results of the TCS network and species distribution model suggested that the wild population TQ located in Sichuan province could serve as the ancestor of cultivated O. japonicus, which was supported by RASP analysis. CONCLUSION: These results suggest that cultivated O. japonicus has experienced dramatic loss of genetic diversity under anthropogenic influence. The genetic differentiation between CMD and ZMD is likely to be influenced by founder effect and strong artificial selection for plant traits. It appears that wild populations in Sichuan area are involved in the origin of not only CMD but also ZMD. In addition, we also raise some suggestions for planning scientific strategies for resource conservation of O. japonicus based on its genetic diversity and population structure.
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DNA de Cloroplastos , Ophiopogon , DNA de Cloroplastos/genética , Filogeografia , Filogenia , Ophiopogon/química , Ophiopogon/genética , Haplótipos/genética , Variação GenéticaRESUMO
Ligands are indispensable for perovskite nanocrystals (NCs) throughout the whole lifetime, as they not only play key roles in the controllable synthesis of NCs with different sizes and shapes, but also act as capping shell that affects optical properties and electrical coupling of NCs. Establishing a systematic understanding of the relationship between ligands and perovskite NCs is significant to enable many potential applications of NCs. This review mainly focuses on the influence of ligands on perovskite NCs. First of all, the ligands-dominated size and shape control of NCs is discussed. Whereafter, the surface defects of NCs and the bonding between ligands and perovskite NCs are classified, and corresponding post-treatment of surface defects via ligands is also summarized. Furthermore, advances in engineering the ligands towards the high performance of optoelectronic devices based on perovskite NCs, including photodetector, solar cell, light emitting diode (LED), and laser, and finally to potential challenges are also discussed.
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BACKGROUND: The nuclear factor kappa B (NFκB) regulatory pathways downstream of tumor necrosis factor (TNF) play a critical role in carcinogenesis. However, the widespread influence of NFκB in cells can result in off-target effects, making it a challenging therapeutic target. Ensemble learning is a machine learning technique where multiple models are combined to improve the performance and robustness of the prediction. Accordingly, an ensemble learning model could uncover more precise targets within the NFκB/TNF signaling pathway for cancer therapy. METHODS: In this study, we trained an ensemble learning model on the transcriptome profiles from 16 cancer types in the TCGA database to identify a robust set of genes that are consistently associated with the NFκB/TNF pathway in cancer. Our model uses cancer patients as features to predict the genes involved in the NFκB/TNF signaling pathway and can be adapted to predict the genes for different cancer types by switching the cancer type of patients. We also performed functional analysis, survival analysis, and a case study of triple-negative breast cancer to demonstrate our model's potential in translational cancer medicine. RESULTS: Our model accurately identified genes regulated by NFκB in response to TNF in cancer patients. The downstream analysis showed that the identified genes are typically involved in the canonical NFκB-regulated pathways, particularly in adaptive immunity, anti-apoptosis, and cellular response to cytokine stimuli. These genes were found to have oncogenic properties and detrimental effects on patient survival. Our model also could distinguish patients with a specific cancer subtype, triple-negative breast cancer (TNBC), which is known to be influenced by NFκB-regulated pathways downstream of TNF. Furthermore, a functional module known as mononuclear cell differentiation was identified that accurately predicts TNBC patients and poor short-term survival in non-TNBC patients, providing a potential avenue for developing precision medicine for cancer subtypes. CONCLUSIONS: In conclusion, our approach enables the discovery of genes in NFκB-regulated pathways in response to TNF and their relevance to carcinogenesis. We successfully categorized these genes into functional groups, providing valuable insights for discovering more precise and targeted cancer therapeutics.
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NF-kappa B , Neoplasias de Mama Triplo Negativas , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/uso terapêutico , Transdução de Sinais/genética , Carcinogênese , Aprendizado de MáquinaRESUMO
Drought stress limits wheat production and threatens food security world-wide. While ethylene-responsive factors (ERFs) are known to regulate plant response to drought stress, the regulatory mechanisms responsible for a tolerant phenotype remain unclear. Here, we describe the positive regulatory role of TaERF87 in mediating wheat tolerance to drought stress. TaERF87 overexpression (OE) enhances drought tolerance, while silencing leads to drought sensitivity in wheat. RNA sequencing with biochemical assays revealed that TaERF87 activates the expression of the proline biosynthesis genes TaP5CS1 and TaP5CR1 via direct binding to GCC-box elements. Furthermore, proline accumulates to higher levels in TaERF87- and TaP5CS1-OE lines than that in wild-type plants under well-watered and drought stress conditions concomitantly with enhanced drought tolerance in these transgenic lines. Moreover, the interaction between TaERF87 and the bHLH transcription factor TaAKS1 synergistically enhances TaP5CS1 and TaP5CR1 transcriptional activation. TaAKS1 OE also increases wheat drought tolerance by promoting proline accumulation. Additionally, our findings verified that TaERF87 and TaAKS1 are targets of abscisic acid-responsive element binding factor 2 (TaABF2). Together, our study elucidates the mechanisms underlying a positive response to drought stress mediated by the TaABF2-TaERF87/TaAKS1-TaP5CS1/TaP5CR1 module, and identifies candidate genes for the development of elite drought-tolerant wheat varieties.
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Secas , Triticum , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Prolina/metabolismo , Estresse Fisiológico/genética , Triticum/metabolismo , Resistência à SecaRESUMO
In recent years, there has been a growing demand for luminescence anticounterfeiting materials that possess the properties of environmentally friendly, single-component, and multimode fluorescence. Among the materials explored, the low dimensional metal halides have gained wide attention because of unique characteristics including low toxicity, simple synthesis, good stability, and so on. Here, we synthesized Mn2+ and Sb3+ codoped Cs2ZnCl4 single crystals by a facile hydrothermal method. Under 365 nm excitation, the codoped compound exhibits dual-band emissions at 530 and 730 nm. However, under 316 nm excitation, the compound only shows one emission band from 500 to 850 nm peaking at 730 nm, while under 460 nm excitation, the emission from 500 to 650 nm with an emission peak at 530 nm can be observed. Based on the study of the photoluminescence mechanism, the green and red emissions originate from the Mn2+ located in the tetrahedron and self-trapped exciton emission of [SbCl4]- clusters, respectively. Due to the zero-dimensional structure of the Cs2ZnCl4 host, there is minimal energy transfer between these dopants. Consequently, the luminous ratios of the two emissions can be independently regulated. Except by tuning the dopant concentrations, the Cs2ZnCl4:Mn2+, Sb3+ demonstrates excitation-wavelength-dependent properties, which could emit more than two colors with the change of excitation wavelength. As a result, multimode anticounterfeiting based on Cs2ZnCl4:Mn2+, Sb3+ crystals has been designed, which aligns with the requirements of environmentally friendly, single-component, and multimode fluorescence properties.
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In this paper, the sesame residue, a common biomass waste, was used as a precursor to synthesize N,O co-doped porous carbon materials via a simple pre-carbonization and KNO3activation two-step strategy. The apparent morphology and supercapacitor performance of the obtained materials can be regulated by changing the pre-carbonization temperature (0 °C, 300 °C and 600 °C). The consequences demonstrate that a large number of C-C and C-O bonds in sesame residue undergo cleavage and form abundant pore structure at the pre-carbonization temperature of 300 °C. After KNO3activation, the material has a moderate specific surface area (1073.4 m2g-1) and affluent heteroatom content (N: 7.52 at%, O: 17.65 at%). As a result, the SS-300 electrode displays exceptional capacitive performance (specific capacitance up to 312.7 F g-1at 0.5 A g-1) and outstanding cyclic stability (capacitance retention reaching 98.3% at 10 A g-1after 8000 charge-discharge cycles). Moreover, the symmetric supercapacitor assembled by SS-300 exhibits high energy densities in both 6 M KOH (4.58 Wh kg-1) and 1 M Na2SO4(15.60 Wh kg-1), highlighting the potential of this material for energy storage applications.
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BACKGROUND: Dysregulated apoptosis of penile mesenchymal cells during male urethragenesis has been previously demonstrated to underly hypospadiac urethral closure failure, and androgen receptor (AR) has been shown to play a central role in regulating penile mesenchyme cell proliferation and survival. However, the regulatory mechanisms upstream and downstream of AR remain poorly understood. Our clinical data and bioinformatics analysis previously indicated that hsa_circ_0000417, a circRNA significantly downregulated in hypospadias preputial specimens, may act as a ceRNA for AR via sequestering hsa_miR-6756-5p, and that the biological functions of hsa_circ_0000417 may significantly involve the PI3K/AKT pathway. In this study, we employed human foreskin fibroblasts (HFF-1) to experimentally validate this putative hsa_circ_0000417/miR-6756-5p/AR axis and its impact on penile mesenchymal cell proliferation and apoptosis. METHOD AND RESULTS: We showed that hsa_circ_0000417 knockdown significantly promoted proliferation and suppressed apoptosis of HFF-1 cells. Mechanistically, hsa_circ_0000417 functioned as a molecular sponge for miR-6756-5p in HFF-1 cells and relieved the latter's translational repression on AR mRNA, leading to decreased AKT activation and increased expression of pro-apoptotic proteins BAX and cleaved-caspase 9. Conversely, elevated levels of miR-6756-5p resulted in diminished AR expression concomitant with enhanced AKT activation and HFF-1 cell proliferation. CONCLUSIONS: Collectively, our data describe for the first time a circRNA-mediated post-transcriptional regulatory mechanism of AR and its functional consequences in penile mesenchymal cells in the context of hypospadias. These findings may contribute to advancing our current understanding of the roles of AR and mesenchymal cell fate decisions during penile morphogenesis.