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OBJECTIVE: In Guangdong Province, hepatitis C virus (HCV) had been found to confer resistance to direct-acting antivirals (DAAs). There were few studies of HCV subtypes and resistance-associated substitutions (RASs) of HCV in different high-risk populations. In this study, we aimed to determine the subtype distribution and the RASs in high-risk population groups, including drug users (DU), men who have sex with men (MSM), female sex workers (FSW), and male patients with sexually transmitted diseases (STD) in Guangdong Province (a highly developed province with a large population). METHODS: Using a city-based sampling strategy,1356 samples were obtained from different population groups. Phylogenetic analyses determined subtypes based on Core, NS5B, or NS5A sequences. HCV subtype distribution and RASs in various risk groups and regions were analyzed. RESULTS: Ten subtypes, of which 6 h and 6 k were novel in Guangdong, were identified. The primary subtype among all risk groups was 6a. RASs in 1b and 3a were different from those observed in other studies. Subtype 3b in western Guangdong was higher than the other three regions. No RASs were found in 6a or any other genotype 6. CONCLUSIONS: The HCV subtypes are expanding in high-risk populations in Guangdong. Drug use by other risk groups and commercial sex by DU may bridge the dissemination of 6a from DU to other populations. The RAS profiles of 1b and 3a differed from those reported in studies conducted in southwestern China. Further research is required to determine the reason for this discrepancy. Moreover, the combination of RASs was high in subtype 3b. To guide HCV treatment of subtype 3b, pretreatment subtyping of HCV genotype 3 should be considered in western cities in the near future.
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Over the past few decades, significant improvements in maize yield have been largely attributed to increased plant density of upright hybrid varieties rather than increased yield per plant. However, dense planting triggers shade avoidance responses (SARs) that optimize light absorption but impair plant vigor and performance, limiting yield improvement through increasing plant density. In this study, we demonstrated that high-density-induced leaf angle narrowing and stem/stalk elongation are largely dependent on phytochrome B (phyB1/B2), the primary photoreceptor responsible for perceiving red (R) and far-red (FR) light in maize. We found that maize phyB physically interacts with the LIGULELESS1 (LG1), a classical key regulator of leaf angle, to coordinately regulate plant architecture and density tolerance. The abundance of LG1 is significantly increased by phyB under high R:FR light (low density) but rapidly decreases under low R:FR light (high density), correlating with variations in leaf angle and plant height under various densities. In addition, we identified the homeobox transcription factor HB53 as a target co-repressed by both phyB and LG1 but rapidly induced by canopy shade. Genetic and cellular analyses showed that HB53 regulates plant architecture by controlling the elongation and division of ligular adaxial and abaxial cells. Taken together, these findings uncover the phyB-LG1-HB53 regulatory module as a key molecular mechanism governing plant architecture and density tolerance, providing potential genetic targets for breeding maize hybrid varieties suitable for high-density planting.
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Fitocromo B , Proteínas de Plantas , Zea mays , Zea mays/crecimiento & desarrollo , Zea mays/genética , Zea mays/metabolismo , Zea mays/efectos de la radiación , Fitocromo B/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/efectos de la radiación , LuzRESUMEN
Plants possess diverse cell types and intricate regulatory mechanisms to adapt to the ever-changing environment of nature. Various strategies have been employed to study cell types and their developmental progressions, including single-cell sequencing methods which provide high-dimensional catalogs to address biological concerns. In recent years, single-cell sequencing technologies in transcriptomics, epigenomics, proteomics, metabolomics, and spatial transcriptomics have been increasingly used in plant science to reveal intricate biological relationships at the single-cell level. However, the application of single-cell technologies to plants is more limited due to the challenges posed by cell structure. This review outlines the advancements in single-cell omics technologies, their implications in plant systems, future research applications, and the challenges of single-cell omics in plant systems.
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Genómica , Metabolómica , Plantas , Proteómica , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Plantas/genética , Plantas/metabolismo , Metabolómica/métodos , Proteómica/métodos , Genómica/métodos , Epigenómica/métodos , Transcriptoma/genéticaRESUMEN
To decipher the genetic diversity within the cucurbit genus Citrullus, we generated telomere-to-telomere (T2T) assemblies of 27 distinct genotypes, encompassing all seven Citrullus species. This T2T super-pangenome has expanded the previously published reference genome, T2T-G42, by adding 399.2 Mb and 11,225 genes. Comparative analysis has unveiled gene variants and structural variations (SVs), shedding light on watermelon evolution and domestication processes that enhanced attributes such as bitterness and sugar content while compromising disease resistance. Multidisease-resistant loci from Citrullus amarus and Citrullus mucosospermus were successfully introduced into cultivated Citrullus lanatus. The SVs identified in C. lanatus have not only been inherited from cordophanus but also from C. mucosospermus, suggesting additional ancestors beyond cordophanus in the lineage of cultivated watermelon. Our investigation substantially improves the comprehension of watermelon genome diversity, furnishing comprehensive reference genomes for all Citrullus species. This advancement aids in the exploration and genetic enhancement of watermelon using its wild relatives.
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Citrullus , Genoma de Planta , Telómero , Citrullus/genética , Telómero/genética , Fitomejoramiento/métodos , Variación Genética , Filogenia , Domesticación , GenotipoRESUMEN
Leaf angle (LA) is a crucial factor that affects planting density and yield in maize. However, the regulatory mechanisms underlying LA formation remain largely unknown. In this study, we performed a comparative histological analysis of the ligular region across various maize inbred lines and revealed that LA is significantly influenced by a two-step regulatory process involving initial cell elongation followed by subsequent lignification in the ligular adaxial sclerenchyma cells (SCs). Subsequently, we performed both bulk and single-nucleus RNA sequencing, generated a comprehensive transcriptomic atlas of the ligular region, and identified numerous genes enriched in the hypodermal cells that may influence their specialization into SCs. Furthermore, we functionally characterized two genes encoding atypical basic-helix-loop-helix (bHLH) transcription factors, bHLH30 and its homolog bHLH155, which are highly expressed in the elongated adaxial cells. Genetic analyses revealed that bHLH30 and bHLH155 positively regulate LA expansion, and molecular experiments demonstrated their ability to activate the transcription of genes involved in cell elongation and lignification of SCs. These findings highlight the specialized functions of ligular adaxial SCs in LA regulation by restricting further extension of ligular cells and enhancing mechanical strength. The transcriptomic atlas of the ligular region at single-nucleus resolution not only deepens our understanding of LA regulation but also enables identification of numerous potential targets for optimizing plant architecture in modern maize breeding.
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Regulación de la Expresión Génica de las Plantas , Hojas de la Planta , Proteínas de Plantas , Zea mays , Zea mays/genética , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Zea mays/citología , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilación de la Expresión Génica , Transcriptoma/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/genéticaRESUMEN
Chili pepper (Capsicum) is known for its unique fruit pungency due to the presence of capsaicinoids. The evolutionary history of capsaicinoid biosynthesis and the mechanism of their tissue specificity remain obscure due to the lack of high-quality Capsicum genomes. Here, we report two telomere-to-telomere (T2T) gap-free genomes of C. annuum and its wild nonpungent relative C. rhomboideum to investigate the evolution of fruit pungency in chili peppers. We precisely delineate Capsicum centromeres, which lack high-copy tandem repeats but are extensively invaded by CRM retrotransposons. Through phylogenomic analyses, we estimate the evolutionary timing of capsaicinoid biosynthesis. We reveal disrupted coding and regulatory regions of key biosynthesis genes in nonpungent species. We also find conserved placenta-specific accessible chromatin regions, which likely allow for tissue-specific biosynthetic gene coregulation and capsaicinoid accumulation. These T2T genomic resources will accelerate chili pepper genetic improvement and help to understand Capsicum genome evolution.
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Capsaicina , Capsicum , Evolución Molecular , Genoma de Planta , Filogenia , Telómero , Capsicum/genética , Capsicum/metabolismo , Capsaicina/metabolismo , Telómero/genética , Telómero/metabolismo , Frutas/genética , Frutas/metabolismo , Retroelementos/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
Coding transcript-derived siRNAs (ct-siRNAs) produced from specific endogenous loci can suppress the translation of their source genes to balance plant growth and stress response. In this study, we generated Arabidopsis mutants with deficiencies in RNA decay and/or post-transcriptional gene silencing (PTGS) pathways and performed comparative sRNA-seq analysis, revealing that multiple RNA decay and PTGS factors impede the ct-siRNA selective production. Genes that produce ct-siRNAs often show increased or unchanged expression and typically have higher GC content in sequence composition. The growth and development of plants can perturb the dynamic accumulation of ct-siRNAs from different gene loci. Two nitrate reductase genes, NIA1 and NIA2, produce massive amounts of 22-nt ct-siRNAs and are highly expressed in a subtype of mesophyll cells where DCL2 exhibits higher expression relative to DCL4, suggesting a potential role of cell-specific expression of ct-siRNAs. Overall, our findings unveil the multifaceted factors and features involved in the selective production and regulation of ct-siRNAs and enrich our understanding of gene silencing process in plants.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Proteínas de Arabidopsis/metabolismo , Interferencia de ARN , ARN Bicatenario/metabolismo , Plantas/metabolismoRESUMEN
Indirect mechanisms of cancer immunotherapies result in delayed treatment effects that vary among patients. Consequently, the use of the log-rank test in trial design and analysis can lead to significant power loss and pose additional challenges for interim decisions in adaptive designs. In this paper, we describe patients' survival using a piecewise proportional hazard model with random lag time and propose an adaptive promising zone design for cancer immunotherapy with heterogeneous delayed effects. We provide solutions for calculating conditional power and adjusting the critical value for the log-rank test with interim data. We divide the sample space into three zones - unfavourable, promising, and favourable -based on re-estimations of the survival parameters, the log-rank test statistic at the interim analysis, and the initial and maximum sample sizes. If the interim results fall into the promising zone, the sample size is increased; otherwise, it remains unchanged. We show through simulations that our proposed approach has greater overall power than the fixed sample design and similar power to the matched group sequential trial. Furthermore, we confirm that critical value adjustment effectively controls the type I error rate inflation. Finally, we provide recommendations on the implementation of our proposed method in cancer immunotherapy trials.
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The delayed treatment effect is a common feature of immunotherapy, characterized by a gradual onset of action ranging from no effect to full effect. In this study, we propose a generalized delayed treatment effect function to depict the delayed effective process precisely and flexibly. To reduce potential power loss caused by the delayed treatment effect in a group sequential trial, we employ the maximin efficiency robust test, which enhances power robustness across a range of possible delays. We present novel approaches based on the Markov chain method for determining group sequential boundaries, calculating the power function, and estimating the maximum sample size through iterative regressions between the square root of the maximum sample size and the normal quantile of power. Extensive simulation studies validate the effectiveness of our approaches, particularly in balanced trials, demonstrating the validity of group sequential boundaries and the accuracy of maximum sample size estimations. Additionally, we utilize a real trial as an example to compare our considered trial with group sequential trials using the log-rank and generalized piecewise weighted log-rank tests. The results show significantly reduced maximum sample sizes, highlighting the economic advantage of our approach.
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Inmunoterapia , Retraso del Tratamiento , Humanos , Simulación por Computador , Inmunoterapia/métodos , Proyectos de Investigación , Tamaño de la MuestraRESUMEN
Light serves as the energy source for plants as well as a signal for growth and development during their whole life cycle. Seedling de-etiolation is the most dramatic manifestation of light-regulated plant development processes, as massive reprogramming of the plant transcriptome occurs at this time. Although several studies have reported about organ-specific development and expression induced by light, a systematic analysis of cell-type-specific differentiation and the associated transcriptional regulation is still lacking. Here we obtained single-cell transcriptional atlases for etiolated, de-etiolating and light-grown Arabidopsis thaliana seedlings. Informative cells from shoot and root tissues were grouped into 48 different cell clusters and finely annotated using multiple markers. With the determination of comprehensive developmental trajectories, we demonstrate light modulation of cell fate determination during guard cell specialization and vasculature development. Comparison of expression atlases between wild type and the pifq mutant indicates that phytochrome-interacting factors (PIFs) are involved in distinct developmental processes in endodermal and stomatal lineage cells via controlling cell-type-specific expression of target genes. These results provide information concerning the light signalling networks at the cell-type resolution, improving our understanding of how light regulates plant development at the cell-type and genome-wide levels. The obtained information could serve as a valuable resource for comprehensively investigating the molecular mechanism of cell development and differentiation in response to light.
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Proteínas de Arabidopsis , Arabidopsis , Fitocromo , Arabidopsis/metabolismo , Plantones , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Tiempo , Fitocromo/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
BACKGROUND: Vitamin D deficiency (VDD) is a public health problem. The variation in vitamin D status across regions and populations remains unclear, and there is a lack of consensus regarding the screening for VDD in individuals. METHODS: Children who visited the hospital from January 2019 to December 2020 were included in this study. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured using an enzyme-linked immunosorbent assay. The cutoffs for serum 25(OH)D concentrations to define deficiency, insufficiency, and sufficiency were < 20 ng/mL, 20-30 ng/mL, and ≥ 30 ng/mL, respectively. RESULTS: A total of 7285 children aged 0-11 years were assessed; the mean 25(OH)D level was 31.4 ng/mL, and the median 25(OH)D level was 30.7 (interquartile range 24.4, 37.5) ng/mL. The 25(OH)D level declined with age in clinical visiting children aged 0-11 years, but maintained a consistently high level in health examination children aged 4-11 years. The percentages of 25(OH)D < 20 ng/mL and 25(OH)D < 30 ng/mL were 10.0% and 43.8%, respectively. Higher percentages of VDD were found in clinical visiting children than in health examination children within the 6-11-year group (53.3% vs. 14.7%) and winter (44.3% vs. 15.4%). CONCLUSION: Low vitamin D status (deficiency and insufficiency) was more common in clinic-visiting children than in health examinations, especially in schoolchildren and in the winter. The study implies the positive effects of vitamin D assessments included in child health checkups to optimize vitamin D status.
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Deficiencia de Vitamina D , Vitamina D , Niño , Lactante , Humanos , Estudios Transversales , China/epidemiología , Prevalencia , Vitaminas , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Callus is a reprogrammed cell mass involved in plant regeneration and gene transformation in crop engineering. Pluripotent callus cells develop into fertile shoots through shoot regeneration. The molecular basis of the shoot regeneration process in crop callus remains largely elusive. This study pioneers the exploration of the spatial transcriptome of tomato callus during shoot regeneration. The findings reveal the presence of highly heterogeneous cell populations within the callus, including epidermis, vascular tissue, shoot primordia, inner callus, and outgrowth shoots. By characterizing the spatially resolved molecular features of shoot primordia and surrounding cells, specific factors essential for shoot primordia formation are identified. Notably, chlorenchyma cells, enriched in photosynthesis-related processes, play a crucial role in promoting shoot primordia formation and subsequent shoot regeneration. Light is shown to promote shoot regeneration by inducing chlorenchyma cell development and coordinating sugar signaling. These findings significantly advance our understanding of the cellular and molecular aspects of shoot regeneration in tomato callus and demonstrate the immense potential of spatial transcriptomics in plant biology.
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Solanum lycopersicum , Solanum lycopersicum/genética , Transcriptoma , Células Epiteliales , Perfilación de la Expresión Génica , Regeneración/genéticaRESUMEN
In this paper, we propose DeepTree, a novel method for modeling trees based on learning developmental rules for branching structures instead of manually defining them. We call our deep neural model "situated latent" because its behavior is determined by the intrinsic state -encoded as a latent space of a deep neural model- and by the extrinsic (environmental) data that is "situated" as the location in the 3D space and on the tree structure. We use a neural network pipeline to train a situated latent space that allows us to locally predict branch growth only based on a single node in the branch graph of a tree model. We use this representation to progressively develop new branch nodes, thereby mimicking the growth process of trees. Starting from a root node, a tree is generated by iteratively querying the neural network on the newly added nodes resulting in the branching structure of the whole tree. Our method enables generating a wide variety of tree shapes without the need to define intricate parameters that control their growth and behavior. Furthermore, we show that the situated latents can also be used to encode the environmental response of tree models, e.g., when trees grow next to obstacles. We validate the effectiveness of our method by measuring the similarity of our tree models and by procedurally generated ones based on a number of established metrics for tree form.
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Motivation: Direct RNA-seq (dRNA-seq) using Oxford Nanopore Technology (ONT) has revolutionized transcript mapping by offering enhanced precision due to its long-read length. Unlike traditional techniques, dRNA-seq eliminates the need for PCR amplification, reducing the impact of GC bias, and preserving valuable base physical information, such as RNA modification and poly(A) length estimation. However, the rapid advancement of ONT devices has set higher standards for analytical software, resulting in potential challenges of software incompatibility and reduced efficiency. Results: We present a novel workflow, called FASTdRNA, to manipulate dRNA-seq data efficiently. This workflow comprises two modules: a data preprocessing module and a data analysis module. The preprocessing data module, dRNAmain, encompasses basecalling, mapping, and transcript counting, which are essential for subsequent analyses. The data analysis module consists of a range of downstream analyses that facilitate the estimation of poly(A) length, prediction of RNA modifications, and assessment of alternative splicing events across different conditions with duplication. The FASTdRNA workflow is designed for the Snakemake framework and can be efficiently executed locally or in the cloud. Comparative experiments have demonstrated its superior performance compared to previous methods. This innovative workflow enhances the research capabilities of dRNA-seq data analysis pipelines by optimizing existing processes and expanding the scope of analysis. Availability and implementation: The workflow is freely available at https://github.com/Tomcxf/FASTdRNA under an MIT license. Detailed install and usage guidance can be found in the GitHub repository.
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The variation in vitamin D status is still unclear. We aim to describe the vitamin D status among healthy infants and children in Shanghai (31° N latitude), one of the largest cities in China. We conducted a hospital-based, 2-year retrospective observational study and recruited children for health examination at the Tongren Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 2019 to December 2020. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured using an enzyme-linked immunosorbent assay. A total of 6164 children aged 0-11 years were included. Of these, 94.4% of the serum 25(OH)D measurements at first assessment were within the range of 12-50 ng/mL. The median 25(OH)D level was 31.3 (IQR 25.6, 38.1) ng/mL, the percentages of 25(OH)D < 20 ng/mL and 25(OH)D < 30 ng/mL were 10.0% and 43.8%, respectively. Low vitamin D status (deficiency and insufficiency) differed significantly by age group (infants, toddlers, preschoolers, and schoolers) and seasonality (all p < .001), but not by gender. For the sub-group (n = 855) of children with repeated assessments, their low 25(OH)D levels increased significantly whether after about a 7-month (n = 351) or 12-month (n = 504) interval, and the increments of median 25(OH)D levels were 8.1 ng/mL and 2.1 ng/mL respectively (p < .001). This study documents the vitamin D status in Shanghai, showing that low vitamin D status is common in infants and children and suggesting that the assessment of 25(OH)D level is necessary for individuals who are at risk for deficiency or excess.
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Recently, the US Food and Drug Administration Oncology Center of Excellence initiated Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development. The agency pointed out that the current paradigm for dose selection-based on the maximum tolerated dose (MTD)-is not sufficient for molecularly targeted therapies and immunotherapies, for which efficacy may not increase after the dose reaches a certain level. In these cases, it is more appropriate to identify the optimal biological dose (OBD) that optimizes the risk-benefit tradeoff of the drug. Project Optimus has spurred tremendous interest and urgent need for guidance on designing dose optimization trials. In this article, we review several representative dose optimization designs, including model-based and model-assisted designs, and compare their operating characteristics based on 10,000 randomly generated scenarios with various dose-toxicity and dose-efficacy curves and some fixed representative scenarios. The results show that, compared with model-based designs, model-assisted methods have advantages of easy-to-implement, robustness, and high accuracy to identify OBD. Some guidance is provided to help biostatisticians and clinicians to choose appropriate dose optimization methods in practice.
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Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Oncología Médica , Proyectos de Investigación , Inmunoterapia , Dosis Máxima Tolerada , Simulación por Computador , Teorema de Bayes , Antineoplásicos/efectos adversosRESUMEN
Estuarine ecosystems undergo pronounced and intricate changes due to the mixing of freshwater and saltwater. Additionally, urbanization and population growth in estuarine regions result in shifts in the planktonic bacterial community and the accumulation of antibiotic resistance genes (ARGs). The dynamic changes in bacterial communities, environmental factors, and carriage of ARGs from freshwater to seawater, as well as the complex interrelationships among these factors, have yet to be fully elucidated. Here, we conducted a comprehensive study based on metagenomic sequencing and full-length 16S rRNA sequencing, covering the entire Pearl River Estuary (PRE) in Guangdong, China. The abundance and distribution of the bacterial community, ARGs, mobile genetic elements (MGEs), and bacterial virulence factors (VFs) were analyzed on a site-by-site basis through sampling along the salinity gradient in PRE, from upstream to downstream. The structure of the planktonic bacterial community undergoes continuous changes in response to variations in estuarine salinity, with the phyla Proteobacteria and Cyanobacteria being dominant bacterial throughout the entire region. The diversity and abundance of ARGs and MGEs gradually decreased with the direction of water flow. A large number of ARGs were carried by potentially pathogenic bacteria, especially in Alpha-proteobacteria and Beta-proteobacteria. Multi-drug resistance genes have the highest abundance and subtypes in PRE. In addition, ARGs are more linked to some MGEs than to specific bacterial taxa and disseminate mainly by HGT and not by vertical transfer in the bacterial communities. Various environmental factors, such as salinity and nutrient concentrations, have a significantly impact on the community structure and distribution of bacteria. In conclusion, our results represent a valuable resource for further investigating the intricate interplay between environmental factors and anthropogenic disturbances on bacterial community dynamics. Moreover, they contribute to a better understanding of the relative impact of these factors on the dissemination of ARGs.
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Estuarios , Genes Bacterianos , Ecosistema , Salinidad , ARN Ribosómico 16S/genética , Bacterias/genética , ChinaRESUMEN
Carotenoids are major accessory pigments in the chloroplast, and they also act as phytohormones and volatile compound precursors to influence plant development and confer characteristic colours, affecting both the aesthetic and nutritional value of fruits. Carotenoid pigmentation in ripening fruits is highly dependent on developmental trajectories. Transcription factors incorporate developmental and phytohormone signalling to regulate the biosynthesis process. By contrast to the well-established pathways regulating ripening-related carotenoid biosynthesis in climacteric fruit, carotenoid regulation in non-climacteric fruit is poorly understood. Capsanthin is the primary carotenoid of non-climacteric pepper (Capsicum) fruit; its biosynthesis is tightly associated with fruit ripening, and it confers red pigmentation to the ripening fruit. In the present study, using a coexpression analysis, we identified an R-R-type MYB transcription factor, DIVARICATA1, and demonstrated its role in capsanthin biosynthesis. DIVARICATA1 encodes a nucleus-localised protein that functions primarily as a transcriptional activator. Functional analyses showed that DIVARICATA1 positively regulates carotenoid biosynthetic gene (CBG) transcript levels and capsanthin levels by directly binding to and activating CBG promoter transcription. Furthermore, an association analysis revealed a significant positive association between DIVARICATA1 transcription level and capsanthin content. ABA promotes capsanthin biosynthesis in a DIVARICATA1-dependent manner. Comparative transcriptomic analysis of DIVARICATA1 in Solanaceae plants showed that its function likely differs among species. Moreover, the pepper DIVARICATA1 gene could be regulated by the ripening regulator MADS-RIN. The present study illustrates the transcriptional regulation of capsanthin biosynthesis and offers a target for breeding peppers with high red colour intensity.
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Capsicum , Factores de Transcripción/metabolismo , Carotenoides/metabolismo , Pigmentos Biológicos/metabolismo , Capsicum/genética , Capsicum/metabolismo , Color , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiones Promotoras Genéticas , Transactivadores/genética , FilogeniaRESUMEN
Although accumulating evidence has highlighted the molecular mechanisms by which hTERT promotes tumour cell invasion and metastasis, the molecular mechanisms of the properties enabling hTERT to contribute to invasion and metastasis have not been clearly illustrated. Here, we report that hTERT promotes gastric cancer invasion and metastasis by recruiting p50 to synergistically inhibit PLEKHA7 expression. We observed that the expression of PLEKHA7 in gastric cancer was significantly negatively associated with the TNM stage and lymphatic metastasis and that decreased PLEKHA7 expression dramatically increased invasion and metastasis in gastric cancer cells. Further mechanistic research showed that hTERT directly regulates PLEKHA7 expression by binding p50 and recruiting the hTERT/p50 complex to the PLEKHA7 promoter. Increased hTERT dramatically decreased PLEKHA7 expression and promoted invasion and metastasis in gastric cancer cells. The hTERT-mediated invasion/metastasis properties at least partially depended on PLEKHA7. Our work uncovers a novel molecular mechanism underlying invasion/metastasis in gastric cancer orchestrated by hTERT and p50.