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1.
Plant Biotechnol J ; 21(2): 433-448, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36385569

RESUMEN

Anthocyanin accumulations in the flowers can improve seed production of hybrid lines, and produce higher commodity value in cotton fibre. However, the genetic mechanism underlying the anthocyanin pigmentation in cotton petals is poorly understood. Here, we showed that the red petal phenotype was introgressed from Gossypium bickii through recombination with the segment containing the R3 bic region in the A07 chromosome of Gossypium hirsutum variety LR compared with the near-isogenic line of LW with white flower petals. The cyanidin-3-O-glucoside (Cy3G) was the major anthocyanin in red petals of cotton. A GhTT19 encoding a TT19-like GST was mapped to the R3 bic site associated with red petals via map-based cloning, but GhTT19 homologue gene from the D genome was not expressed in G. hirsutum. Intriguingly, allelic variations in the promoters between GhTT19LW and GhTT19LR , rather than genic regions, were found as genetic causal of petal colour variations. GhTT19-GFP was found localized in both the endoplasmic reticulum and tonoplast for facilitating anthocyanin transport. An additional MYB binding element found only in the promoter of GhTT19LR , but not in that of GhTT19LW , enhanced its transactivation by the MYB activator GhPAP1. The transgenic analysis confirmed the function of GhTT19 in regulating the red flower phenotype in cotton. The essential light signalling component GhHY5 bonded to and activated the promoter of GhPAP1, and the GhHY5-GhPAP1 module together regulated GhTT19 expression to mediate the light-activation of petal anthocyanin pigmentation in cotton. This study provides new insights into the molecular mechanisms for anthocyanin accumulation and may lay a foundation for faster genetic improvement of cotton.


Asunto(s)
Antocianinas , Gossypium , Gossypium/genética , Gossypium/metabolismo , Glutatión Transferasa/metabolismo , Proteínas de Plantas/metabolismo , Flores/genética , Flores/metabolismo , Pigmentación/genética , Regulación de la Expresión Génica de las Plantas/genética
2.
Brief Bioinform ; 22(5)2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-33822890

RESUMEN

Recent pharmacogenomic studies that generate sequencing data coupled with pharmacological characteristics for patient-derived cancer cell lines led to large amounts of multi-omics data for precision cancer medicine. Among various obstacles hindering clinical translation, lacking effective methods for multimodal and multisource data integration is becoming a bottleneck. Here we proposed DeepDRK, a machine learning framework for deciphering drug response through kernel-based data integration. To transfer information among different drugs and cancer types, we trained deep neural networks on more than 20 000 pan-cancer cell line-anticancer drug pairs. These pairs were characterized by kernel-based similarity matrices integrating multisource and multi-omics data including genomics, transcriptomics, epigenomics, chemical properties of compounds and known drug-target interactions. Applied to benchmark cancer cell line datasets, our model surpassed previous approaches with higher accuracy and better robustness. Then we applied our model on newly established patient-derived cancer cell lines and achieved satisfactory performance with AUC of 0.84 and AUPRC of 0.77. Moreover, DeepDRK was used to predict clinical response of cancer patients. Notably, the prediction of DeepDRK correlated well with clinical outcome of patients and revealed multiple drug repurposing candidates. In sum, DeepDRK provided a computational method to predict drug response of cancer cells from integrating pharmacogenomic datasets, offering an alternative way to prioritize repurposing drugs in precision cancer treatment. The DeepDRK is freely available via https://github.com/wangyc82/DeepDRK.


Asunto(s)
Antineoplásicos/uso terapéutico , Biología Computacional/métodos , Aprendizaje Profundo , Reposicionamiento de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Programas Informáticos , Antineoplásicos/química , Línea Celular Tumoral , Conjuntos de Datos como Asunto , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Farmacogenética/métodos , Medicina de Precisión/métodos , Pronóstico , Transcriptoma
3.
Bioorg Chem ; 137: 106617, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37267793

RESUMEN

Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha, and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure-activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 µM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25, and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with KD value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Sorafenib/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/patología , Relación Estructura-Actividad , Células Hep G2 , Proliferación Celular , Apoptosis , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral
4.
BMC Gastroenterol ; 22(1): 244, 2022 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-35568828

RESUMEN

Gastric cancer, or stomach cancer, that originates in the inner lining of the stomach, was the fifth most common cancer and the fourth mortality globally, with over one million new cases in 2020 and an estimated 769,000 deaths. The molecular characteristics of gastric cancer has been complicated by histological and intratumor heterogeneity. The incidence of gastric cancer shows wide geographical variation. As the largest and highest region in China, Qinghai-Tibetan Plateau is one of the important global biodiversity hotspots. Here, we collect tumour and paired normal bio-samples from 31 primary gastric cancer patients from Qinghai Provincial People's Hospital, and discuss the molecular characteristics for gastric cancer patients living in plateau. They have more single nucleotide polymorphisms (SNP) located in chromosome 7 with C → T and G → A as the most common alteration types, barely share the cancer driver genes with western patients, and have no significant differences in various Chinese nation. These characteristics offers a great opportunity to further understanding the divergent mechanism of gastric cancer, increase the efficacy for diagnosis and prognosis, finally lead the optimal targeted therapeutics.


Asunto(s)
Neoplasias Gástricas , China/epidemiología , Geografía , Humanos , Incidencia , Neoplasias Gástricas/genética , Tibet/epidemiología
5.
Molecules ; 26(17)2021 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-34500659

RESUMEN

In this study, broilers were fed with heavy-metal-containing diets (Zn, Cu, Pb, Cr, As, Hg) at three rates (T1: 5 kg premix/ton feed, T2: 10 kg premix/ton feed and T3: 15 kg premix/ton feed) and Doxycycline (DOX) and Gatifloxacin (GAT) at low or high doses (T4: 31.2 mg DOX/bird/day and 78 mg GAT/bird/day, T5: 15.6 mg DOX/bird/day and 48 mg GAT/bird/day) to assess the accumulation of various heavy metals and the fate of two antibiotics in broiler manure after 35 days of aerobic composting. The results indicated that the two antibiotics changed quite differently during aerobic composting. About 14.96-15.84% of Doxycycline still remained at the end of composting, while Gatifloxacin was almost completely removed within 10 days of composting. The half-lives of Doxycycline were 13.75 and 15.86 days, while the half-lives of Gatifloxacin were only 1.32 and 1.38 days. Based on the Redundancy analysis (RDA), the concentration of antibiotics was significantly influenced by physico-chemical properties (mainly temperature and pH) throughout the composting process. Throughout the composting process, all heavy metal elements remained concentrated in organic fertilizer. In this study the Cr content reached 160.16 mg/kg, 223.98 mg/kg and 248.02 mg/kg with increasing premix feed rates, similar to Zn, which reached 258.2 mg/kg, 312.21 mg/kg and 333.68 mg/kg. Zn and Cr concentrations well exceeded the United States and the European soil requirements. This experiment showed that antibiotic residues and the accumulation of heavy metals may lead to soil contamination and pose a risk to the soil ecosystem.


Asunto(s)
Doxiciclina/metabolismo , Gatifloxacina/metabolismo , Animales , Compostaje , Estiércol/microbiología , Metales Pesados/metabolismo
6.
PLoS Comput Biol ; 15(12): e1007540, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31877126

RESUMEN

Long noncoding RNA (lncRNA) transcripts have emerging impacts in cancer studies, which suggests their potential as novel therapeutic agents. However, the molecular mechanism behind their treatment effects is still unclear. Here, we designed a computational model to Associate LncRNAs with Anti-Cancer Drugs (ALACD) based on a bilevel optimization model, which optimized the gene signature overlap in the upper level and imputed the missing lncRNA-gene association in the lower level. ALACD predicts genes coexpressed with lncRNAs mean while matching drug's gene signatures. This model allows us to borrow the target gene information of small molecules to understand the mechanisms of action of lncRNAs and their roles in cancer. The ALACD model was systematically applied to the 10 cancer types in The Cancer Genome Atlas (TCGA) that had matched lncRNA and mRNA expression data. Cancer type-specific lncRNAs and associated drugs were identified. These lncRNAs show significantly different expression levels in cancer patients. Follow-up functional and molecular pathway analysis suggest the gene signatures bridging drugs and lncRNAs are closely related to cancer development. Importantly, patient survival information and evidence from the literature suggest that the lncRNAs and drug-lncRNA associations identified by the ALACD model can provide an alternative choice for cancer targeting treatment and potential cancer pognostic biomarkers. The ALACD model is freely available at https://github.com/wangyc82/ALACD-v1.


Asunto(s)
Modelos Genéticos , Neoplasias/genética , ARN Largo no Codificante/genética , Algoritmos , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Biología Computacional , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Ratones , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , ARN Largo no Codificante/metabolismo , Aprendizaje Automático Supervisado
7.
Nucleic Acids Res ; 45(21): 12100-12112, 2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-29036709

RESUMEN

Alternative splicing (AS) is a genetically and epigenetically regulated pre-mRNA processing to increase transcriptome and proteome diversity. Comprehensively decoding these regulatory mechanisms holds promise in getting deeper insights into a variety of biological contexts involving in AS, such as development and diseases. We assembled splicing (epi)genetic code, DeepCode, for human embryonic stem cell (hESC) differentiation by integrating heterogeneous features of genomic sequences, 16 histone modifications with a multi-label deep neural network. With the advantages of epigenetic features, DeepCode significantly improves the performance in predicting the splicing patterns and their changes during hESC differentiation. Meanwhile, DeepCode reveals the superiority of epigenomic features and their dominant roles in decoding AS patterns, highlighting the necessity of including the epigenetic properties when assembling a more comprehensive splicing code. Moreover, DeepCode allows the robust predictions across cell lineages and datasets. Especially, we identified a putative H3K36me3-regulated AS event leading to a nonsense-mediated mRNA decay of BARD1. Reduced BARD1 expression results in the attenuation of ATM/ATR signalling activities and further the hESC differentiation. These results suggest a novel candidate mechanism linking histone modifications to hESC fate decision. In addition, when trained in different contexts, DeepCode can be expanded to a variety of biological and biomedical fields.


Asunto(s)
Empalme Alternativo , Células Madre Embrionarias/metabolismo , Epigénesis Genética , Código de Histonas , Aprendizaje Automático , Redes Neurales de la Computación , Diferenciación Celular/genética , Línea Celular , Linaje de la Célula , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Análisis de Secuencia de ARN , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
8.
Ecotoxicol Environ Saf ; 171: 12-25, 2019 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-30593996

RESUMEN

Soil salinity is a major abiotic stress affecting crop growth and productivity. Ricinus communis has good salt tolerance and is also an important oilseed crop throughout the world. Early seedling stage (such as cotyledon expansion stage) is the most vulnerable period for plant under stresses. However, little information exist concerning the physiological and molecular mechanisms of Ricinus communis seedlings and the role play by cotyledons and true leaf under salt stress. In the present study, biomass, photosynthesis, chlorophyll fluorescence, inorganic ions and organic solutes contents were measured, and two dimensional gel electrophoresis-based proteomic technology was employed to identify the differentially abundant proteins in the salt-treated Ricinus communis cotyledons and true leaves. The results showed that salt stress reduced growth and photosynthesis in the seedlings. With increasing salinity, the Na+ content increased and K+ content decreased in both cotyledons and leaves, but the true leaves had lower Na+ and higher K+ contents. Soluble sugars and proline are the primary organic solutes to cope with osmotic stress. In addition, proteomic analysis revealed 30 and 42 differentially accumulated protein spots in castor cotyledon and true leaf under salt stress, respectively. Most of the identified proteins were involved in carbohydrate and energy metabolism, photosynthesis, genetic information process, reactive oxygen species metabolism, amino acid metabolism and cell structure. The physiological and proteomic results highlighted that cotyledons accumulated a large number of Na+ and provided more energy to help true leaves cope with salt stress. The true leaves saved carbon structures to synthesize osmotic substances, and the enhancement of chlorophyll synthesis and electron transfer in true leaves could also maintain photosynthesis under salt stress. These findings provide new insights into different physiological mechanisms in cotyledon and true leaf of Ricinus communis response to salt stress during early seedling stage.


Asunto(s)
Cotiledón/metabolismo , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Ricinus , Salinidad , Tolerancia a la Sal , Plantones/metabolismo , Biomasa , Metabolismo Energético , Presión Osmótica/fisiología , Fotosíntesis , Potasio/metabolismo , Prolina/metabolismo , Proteómica , Plantones/crecimiento & desarrollo , Sodio/metabolismo , Cloruro de Sodio/análisis
9.
Bioinformatics ; 32(2): 226-34, 2016 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-26415726

RESUMEN

MOTIVATION: With the booming of interactome studies, a lot of interactions can be measured in a high throughput way and large scale datasets are available. It is becoming apparent that many different types of interactions can be potential drug targets. Compared with inhibition of a single protein, inhibition of protein-protein interaction (PPI) is promising to improve the specificity with fewer adverse side-effects. Also it greatly broadens the drug target search space, which makes the drug target discovery difficult. Computational methods are highly desired to efficiently provide candidates for further experiments and hold the promise to greatly accelerate the discovery of novel drug targets. RESULTS: Here, we propose a machine learning method to predict PPI targets in a genomic-wide scale. Specifically, we develop a computational method, named as PrePPItar, to Predict PPIs as drug targets by uncovering the potential associations between drugs and PPIs. First, we survey the databases and manually construct a gold-standard positive dataset for drug and PPI interactions. This effort leads to a dataset with 227 associations among 63 PPIs and 113 FDA-approved drugs and allows us to build models to learn the association rules from the data. Second, we characterize drugs by profiling in chemical structure, drug ATC-code annotation, and side-effect space and represent PPI similarity by a symmetrical S-kernel based on protein amino acid sequence. Then the drugs and PPIs are correlated by Kronecker product kernel. Finally, a support vector machine (SVM), is trained to predict novel associations between drugs and PPIs. We validate our PrePPItar method on the well-established gold-standard dataset by cross-validation. We find that all chemical structure, drug ATC-code, and side-effect information are predictive for PPI target. Moreover, we can increase the PPI target prediction coverage by integrating multiple data sources. Follow-up database search and pathway analysis indicate that our new predictions are worthy of future experimental validation. CONCLUSION: In conclusion, PrePPItar can serve as a useful tool for PPI target discovery and provides a general heterogeneous data integrative framework. AVAILABILITY AND IMPLEMENTATION: PrePPItar is available at http://doc.aporc.org/wiki/PrePPItar. CONTACT: ycwang@nwipb.cas.cn or ywang@amss.ac.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Descubrimiento de Drogas/métodos , Mapeo de Interacción de Proteínas , Máquina de Vectores de Soporte , Algoritmos , Humanos , Preparaciones Farmacéuticas/química , Proteínas/química , Proteínas/efectos de los fármacos , Análisis de Secuencia de Proteína
10.
Bioinformatics ; 29(10): 1317-24, 2013 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-23564845

RESUMEN

MOTIVATION: Discovering drug's Anatomical Therapeutic Chemical (ATC) classification rules at molecular level is of vital importance to understand a vast majority of drugs action. However, few studies attempt to annotate drug's potential ATC-codes by computational approaches. RESULTS: Here, we introduce drug-target network to computationally predict drug's ATC-codes and propose a novel method named NetPredATC. Starting from the assumption that drugs with similar chemical structures or target proteins share common ATC-codes, our method, NetPredATC, aims to assign drug's potential ATC-codes by integrating chemical structures and target proteins. Specifically, we first construct a gold-standard positive dataset from drugs' ATC-code annotation databases. Then we characterize ATC-code and drug by their similarity profiles and define kernel function to correlate them. Finally, we use a kernel method, support vector machine, to automatically predict drug's ATC-codes. Our method was validated on four drug datasets with various target proteins, including enzymes, ion channels, G-protein couple receptors and nuclear receptors. We found that both drug's chemical structure and target protein are predictive, and target protein information has better accuracy. Further integrating these two data sources revealed more experimentally validated ATC-codes for drugs. We extensively compared our NetPredATC with SuperPred, which is a chemical similarity-only based method. Experimental results showed that our NetPredATC outperforms SuperPred not only in predictive coverage but also in accuracy. In addition, database search and functional annotation analysis support that our novel predictions are worthy of future experimental validation. CONCLUSION: In conclusion, our new method, NetPredATC, can predict drug's ATC-codes more accurately by incorporating drug-target network and integrating data, which will promote drug mechanism understanding and drug repositioning and discovery. AVAILABILITY: NetPredATC is available at http://doc.aporc.org/wiki/NetPredATC. CONTACT: ycwang@nwipb.cas.cn or ywang@amss.ac.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Algoritmos , Bases de Datos Farmacéuticas , Sistemas de Liberación de Medicamentos , Preparaciones Farmacéuticas/química , Programas Informáticos
11.
J Theor Biol ; 344: 78-87, 2014 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-24291233

RESUMEN

Post-translational modification (PTM) is the chemical modification of a protein after its translation and one of the later steps in protein biosynthesis for many proteins. It plays an important role which modifies the end product of gene expression and contributes to biological processes and diseased conditions. However, the experimental methods for identifying PTM sites are both costly and time-consuming. Hence computational methods are highly desired. In this work, a novel encoding method PSPM (position-specific propensity matrices) is developed. Then a support vector machine (SVM) with the kernel matrix computed by PSPM is applied to predict the PTM sites. The experimental results indicate that the performance of new method is better or comparable with the existing methods. Therefore, the new method is a useful computational resource for the identification of PTM sites. A unified standalone software PTMPred is developed. It can be used to predict all types of PTM sites if the user provides the training datasets. The software can be freely downloaded from http://www.aporc.org/doc/wiki/PTMPred.


Asunto(s)
Secuencia de Aminoácidos/genética , Biología Computacional/métodos , Procesamiento Proteico-Postraduccional , Diseño de Software , Algoritmos , Animales , Glicosilación , Fosforilación , Fosfotransferasas/genética , Fosfotransferasas/metabolismo , Posición Específica de Matrices de Puntuación , Máquina de Vectores de Soporte
12.
NPJ Syst Biol Appl ; 10(1): 62, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816426

RESUMEN

Individual may response to drug treatment differently due to their genetic variants located in enhancers. These variants can alter transcription factor's (TF) binding strength, affect enhancer's chromatin activity or interaction, and eventually change expression level of downstream gene. Here, we propose a computational framework, PERD, to Predict the Enhancers Responsive to Drug. A machine learning model was trained to predict the genome-wide chromatin accessibility from transcriptome data using the paired expression and chromatin accessibility data collected from ENCODE and ROADMAP. Then the model was applied to the perturbed gene expression data from Connectivity Map (CMAP) and Cancer Drug-induced gene expression Signature DataBase (CDS-DB) and identify drug responsive enhancers with significantly altered chromatin accessibility. Furthermore, the drug responsive enhancers were related to the pharmacogenomics genome-wide association studies (PGx GWAS). Stepping on the traditional drug-associated gene signatures, PERD holds the promise to enhance the causality of drug perturbation by providing candidate regulatory element of those drug associated genes.


Asunto(s)
Cromatina , Estudio de Asociación del Genoma Completo , Aprendizaje Automático , Cromatina/genética , Cromatina/efectos de los fármacos , Humanos , Estudio de Asociación del Genoma Completo/métodos , Elementos de Facilitación Genéticos/genética , Biología Computacional/métodos , Transcriptoma/genética , Transcriptoma/efectos de los fármacos , Factores de Transcripción/genética , Perfilación de la Expresión Génica/métodos , Farmacogenética/métodos
13.
Plants (Basel) ; 13(2)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38256808

RESUMEN

Vegetation on dunes regulates the water supply from the dunes to the inter-dune lowland, which is a crucial factor affecting lake water dynamics in the inter-dune lowland. Previous researchers have paid insufficient attention to the water regulation function of dunes on a landscape- and regional scale. To fill this gap, both remote sensing technology and field observations were used to analyze the variations in the lake area and their influence factors, such as vegetation coverage and precipitation in the lake watershed, on a multi-year scale (2000-2020) and one-year scale (2021), respectively. The results showed that precipitation is the main factor influencing the changes in lake water, and artificial sand vegetation can regulate the changes in lake water. On the multi-year scale, with the coverage of artificial sand-fixing vegetation increasing on sand dunes in the lake watershed, the areas of the lakes were gradually decreasing. On the one-year scale, with dune vegetation coverage increased, the water supply from dunes to lakes showed a decreasing trend. This model can provide a possibility for estimating and predicting the influence of water supply from dunes to lakes that is affected by sand-fixing vegetation. The findings have significant theoretical and practical utility for the rational utilization of water resources in sandy land, as well as for assisting in the selection of an optimized construction mode for desert control projects.

14.
Phytochemistry ; 222: 114100, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38636688

RESUMEN

Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11' and C-5/C-13' linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC50 values ranging from 7.9 to 67.1 µM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC50 values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 µM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of -9.0 kcal/mol by molecular docking and provide KD value of 43.7 µM by Surface Plasmon Resonance assay.


Asunto(s)
Artemisia , Artemisia/química , Humanos , Estructura Molecular , Relación Estructura-Actividad , Sesquiterpenos de Guayano/química , Sesquiterpenos de Guayano/farmacología , Sesquiterpenos de Guayano/aislamiento & purificación , Animales , Dimerización , Simulación del Acoplamiento Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral
15.
Ecol Evol ; 13(1): e9694, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36620410

RESUMEN

Comprising ca. 200 species, Saxifraga sect. Ciliatae is the most species-rich section of Saxifraga s.str., whose center of diversity is in the Tibeto-Himalayan region. The infra-sectional classification of sect. Ciliatae is still in debate due to the high level of species richness, as well as remarkable variations of habitat, morphology, physiology and life cycles. Subdivisions of this section proposed in various taxonomic systems have not been adequately tested in previous phylogenetic studies, partly due to low taxonomic sampling density, but also to the use of few DNA markers. In order to achieve a more robust infra-sectional classification of sect. Ciliatae, complete chloroplast genomes of 94 taxa from this section were analyzed, of which 93 were newly sequenced, assembled and annotated. The length of the 94 plastomes of sect. Ciliatae taxa range from 143,479 to 159,938 bp, encoding 75 to 79 unique protein-coding genes (PCGs). Analyses of the 94 plastomes revealed high conservation in structural organization, gene arrangement, and gene content. Gene loss and changes of IR boundaries were detected but in extremely low frequency. The molecular phylogenetic tree from concatenated PCGs and complete chloroplast genome sequences exhibited high resolution and support values and confirms that sect. Ciliatae is monophyletic. Three well-supported clades were revealed within the section that agree relatively well with the subsectional taxonomy of Gornall (1987), but some minor modifications should be made. Firstly, the monotypic subsection Cinerascentes should be abandoned and its constituent species, S. cinerascens, assigned to subsect. Gemmiparae. Secondly, subsections Rosulares and Serpyllifoliae should be merged and become subsect. Rosulares. Section Ciliatae thus comprises: subsect. Hirculoideae Engl. & Irmsch.; subsect. Rosulares Gornall; subsect. Gemmiparae Engl. & Irmsch.; subsect. Flagellares (C. B. Clarke) Engl. & Irmsch. and subsect. Hemisphaericae (Engl. & Irmsch.) Gornall.

16.
Front Microbiol ; 14: 1110100, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36876101

RESUMEN

Background: The 2009 pandemic H1N1 influenza A virus (pdm09) continue to evolve, and few studies have systemically analyzed the evolution, replication, and transmission of pmd09 viruses in China. Methods: To better understand the evolution and pathogenicity of pdm09 viruses, we systematically analyzed viruses that were confirmed in 2009-2020 in China and characterized their replication and transmission ability. We extensively analyzed the evolution characteristics of pdm/09 in China over the past decades. The replication ability of 6B.1 and 6B.2 lineages on Madin-Darby canine kidney (MDCK) and human lung adenocarcinoma epithelial (A549) cells and their pathogenicity and transmission in guinea pigs were also compared. Results: In total, 3,038 pdm09 viruses belonged to clade 6B.1 (62% of all pdm09 viruses) and clade 6B.2 (4%). Clade 6B.1 pdm09 viruses are the predominant clade, with proportions of 54.1%, 78.9%, 57.2%, 58.6%, 61.7%, 76.3%, and 66.6% in the North, Northeast, East, Central, South, Southwest, and Northeast regions in China, respectively. The isolation proportion of clade 6B.1 pdm/09 viruses was 57.1%, 74.3%, 96.1%, 98.2%, 86.7%, and 78.5% in 2015-2020, respectively. A clear differentiation time point appeared in 2015 before which the evolution trend of pdm09 viruses in China was similar to that in North America but then showed a different trend after that point. To characterize pdm09 viruses in China after 2015, we further analyzed 33 pdm09 viruses isolated in Guangdong in 2016-2017, among which A/ Guangdong/33/2016 and A/Guangdong/184/2016 (184/2016) belonged to clade 6B.2, and the other 31 strains belonged to clade 6B.1. A/Guangdong/887/2017 (887/2017) and A/Guangdong/752/2017 (752/2017) (clade 6B.1), 184/2016 (clade 6B.2) and A/California/04/2009 (CA04) replicated efficiently in MDCK cells and A549 cells, as well as the turbinates of guinea pigs. 184/2016 and CA04 could transmit among guinea pigs through physical contact. Conclusion: Our findings provide novel insights into the evolution, pathogenicity, and transmission of pdm09 virus. The results show that enhancing surveillance of pdm09 viruses and timely evaluation of their virulence are essential.

17.
Front Plant Sci ; 14: 1330664, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38250452

RESUMEN

Introduction: Belowground bud banks play integral roles in vegetation regeneration and ecological succession of plant communities; however, human-caused changes in land use severely threaten their resilience and regrowth. Although vegetation attributes and soil properties mediate such anthropogenic effects, their influence on bud bank size and composition and its regulatory mechanisms under land use change have not been explored. Methods: We conducted a field investigation to examine impacts of land use change on bud bank size and composition, vegetation attributes, and soil properties in wetlands (WL), farmlands (FL), and alpine meadow (AM) ecosystems in Zhejiang Province, China. Results: Overall, 63 soil samples in close proximity to the vegetation quadrats were excavated using a shovel, and samples of the excavated soil were placed in plastic bags for onward laboratory soil analysis. The total bud density (1514.727 ± 296.666) and tiller bud density (1229.090 ± 279.002) in wetland ecosystems were significantly higher than in farmland and alpine meadow ecosystems [i.e., total (149.333 ± 21.490 and 573.647 ± 91.518) and tiller bud density (24.666 ± 8.504 and 204.235 ± 50.550), respectively]. While vegetation attributes critically affected bud banks in WL ecosystems, soil properties strongly influenced bud banks in farmland and alpine meadow ecosystems. In wetland ecosystems, total and tiller buds were predominantly dependent on soil properties, but vegetation density played a significant role in farmlands and alpine meadow ecosystems. Root sprouting and rhizome buds significantly correlated with total C in the top 0 - 10 cm layer of farmland and alpine meadow ecosystems, respectively, and depended mainly on soil properties. Discussion: Our results demonstrate that land use change alters bud bank size and composition; however, such responses differed among bud types in wetland, farmland, and alpine meadow ecosystems.

18.
J Theor Biol ; 315: 64-70, 2012 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-22999977

RESUMEN

The past decades witnessed extensive efforts to study the relationship among proteins. Particularly, sequence-based protein-protein interactions (PPIs) prediction is fundamentally important in speeding up the process of mapping interactomes of organisms. High-throughput experimental methodologies make many model organism's PPIs known, which allows us to apply machine learning methods to learn understandable rules from the available PPIs. Under the machine learning framework, the composition vectors are usually applied to encode proteins as real-value vectors. However, the composition vector value might be highly correlated to the distribution of amino acids, i.e., amino acids which are frequently observed in nature tend to have a large value of composition vectors. Thus formulation to estimate the noise induced by the background distribution of amino acids may be needed during representations. Here, we introduce two kinds of denoising composition vectors, which were successfully used in construction of phylogenetic trees, to eliminate the noise. When validating these two denoising composition vectors on Escherichia coli (E. coli), Saccharomyces cerevisiae (S. cerevisiae) and human PPIs datasets, surprisingly, the predictive performance is not improved, and even worse than non-denoised prediction. These results suggest that the noise in phylogenetic tree construction may be valuable information in PPIs prediction.


Asunto(s)
Mapeo de Interacción de Proteínas , Proteínas/química , Proteínas/metabolismo , Secuencia de Aminoácidos , Área Bajo la Curva , Bases de Datos de Proteínas , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Humanos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
19.
Sci Rep ; 12(1): 18288, 2022 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-36316398

RESUMEN

This study aims to make clear of grassland coverage change and quantitative assessment its effect factors. We collected the data from the National Bureau of Statistics ( http://www.stats.gov.cn ) and "China 20th Century Land Use/Cover Change (LUCC) Spatio-temporal Platform". Grassland coverage area showed an upward trend from 1980 to 1990, and the grassland coverage area is gradually decreasing from 1990 to 2000, and the grassland coverage area has not changed much from 2000 to 2018. The medium-coverage grassland area has the highest correlation with the total population, and the high-coverage grassland area has the lowest correlation with the total population. Land use types and the composite of gross agricultural output have influence on grassland coverage area. It is hoped that relevant policies should consider land use types and ecological benefits while balancing economic development and urban development.


Asunto(s)
Conservación de los Recursos Naturales , Pradera , Agricultura , China , Ecosistema
20.
Sci Total Environ ; 817: 152808, 2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-34982991

RESUMEN

At present, the effect of multiple antibiotics on aerobic composting process and its mechanism are not clear. So in this study, broiler manure containing different doses of Doxycycline (DOX) and Gatifloxacin (GAT) were used as raw materials and mixed with rice hull for aerobic composting, and the effects of the combination of multiple antibiotics on the process parameters of broiler manure composting and the succession of bacterial and fungal community structures were systematically analyzed. Our results showed that at the initial period of composting, the combination of multiple antibiotics led to a delayed temperature and pH increase (T1: 57.0 °C, T2: 48.3 °C, T3: 45.5 °C on Day 3 for temperature and T1: 7.44, T2: 7.1, T3: 6.88 on Day 5 for pH), and a slow total nitrogen decrease (T1: 1.56%, T2: 1.82%, T3: 1.74% on Day 5). Although these effects decreased gradually with the degradation of antibiotics, the relative abundance of Actinobacteriota (T1: 13.29%, T2: 10.57%, T3: 8.99%) and Bacteroidota (T1:27.52%, T2:40.03%, T3:39.81%)) were still influenced by multiple antibiotic residuals until the end of composting period. Higher levels of antibiotics had more lasting effects on the bacterial community (T3 > T2). However, the combination of these two antibiotics did not significantly promote or inhibit the succession of the fungal community structure. The heatmaps showed that composting stage had a greater effect on the microbial community structures than antibiotics. The results provided a theoretical reference for composting broiler manure containing DOX and GAT.


Asunto(s)
Compostaje , Animales , Antibacterianos , Pollos , Estiércol , Suelo
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