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1.
Plant J ; 113(5): 1021-1034, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36602036

RESUMO

Saururus chinensis, an herbaceous magnoliid without perianth, represents a clade of early-diverging angiosperms that have gone through woodiness-herbaceousness transition and pollination obstacles: the characteristic white leaves underneath inflorescence during flowering time are considered a substitute for perianth to attract insect pollinators. Here, using the newly sequenced S. chinensis genome, we revisited the phylogenetic position of magnoliids within mesangiosperms, and recovered a sister relationship for magnoliids and Chloranthales. By considering differentially expressed genes, we identified candidate genes that are involved in the morphogenesis of the white leaves in S. chinensis. Among those genes, we verified - in a transgenic experiment with Arabidopsis - that increasing the expression of the "pseudo-etiolation in light" gene (ScPEL) can inhibit the biosynthesis of chlorophyll. ScPEL is thus likely responsible for the switches between green and white leaves, suggesting that changes in gene expression may underlie the evolution of pollination strategies. Despite being an herbaceous plant, S. chinensis still has vascular cambium and maintains the potential for secondary growth as a woody plant, because the necessary machinery, i.e., the entire gene set involved in lignin biosynthesis, is well preserved. However, similar expression levels of two key genes (CCR and CAD) between the stem and other tissues in the lignin biosynthesis pathway are possibly associated with the herbaceous nature of S. chinensis. In conclusion, the S. chinensis genome provides valuable insights into the adaptive evolution of pollination in Saururaceae and reveals a possible mechanism for the evolution of herbaceousness in magnoliids.


Assuntos
Arabidopsis , Magnoliopsida , Saururaceae , Filogenia , Polinização/genética , Lignina , Magnoliopsida/genética
2.
Bioorg Med Chem Lett ; 36: 127788, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33460739

RESUMO

VEGF/VEGFR-2 signaling plays a critical part in tumor angiogenesis. Inhibition of this pathway has been considered as a promising approach for cancer treatment. In this work, a series of 6,7-dimethoxy-4-anilinoquinazoline derivatives bearing diarylamide moiety were designed, synthesized and evaluated as potent inhibitors of VEGFR-2 kinase. Their in vitro antiproliferation activities against two human cancer cell lines Hep-G2 and MCF-7 have also been determined. Among them, compound 14b exhibited the most potent inhibitory activity against VEGFR-2 with IC50 value of 0.016 ± 0.002 µM and it showed the most potent antiproliferative effect against Hep-G2 and MCF-7 with IC50 values at low-micromolar range. Molecular docking studies revealed that these compounds represented by the most potent compound 14b could bind well to the ATP-binding site of VEGFR-2, which suggested that compound 14b could be a potential anticancer agent targeting VEGFR-2.


Assuntos
Amidas/farmacologia , Antineoplásicos/farmacologia , Descoberta de Drogas , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Amidas/síntese química , Amidas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/química , Relação Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
3.
BMC Public Health ; 18(1): 881, 2018 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-30012126

RESUMO

BACKGROUND: Fatigue is highly prevalent among doctors worldwide. However, no research has been done to examine the associations of emotional intelligence (EI) and emotional labor strategy with fatigue among Chinese doctors. This study aimed to examine whether or not emotional labor strategy mediates the association between EI and fatigue in this occupational group. METHODS: A cross-sectional study was conducted in Shenyang from March to April 2014. A set of self-administered questionnaires was distributed to 950 doctors, including Chalder Fatigue Scale (CFS), Wong and Law Emotional Intelligence Scale (WLEIS) and a 14-item emotional labor scale. Complete responses were obtained from 740 (77.9%) participants. Hierarchical linear regression was performed to examine the associations of EI and emotional labor strategies (surface acting, SA; deep acting, DA; natural acting, NA) with fatigue. Asymptotic and resampling strategies were used to examine the mediating roles of emotional labor strategies. RESULTS: The mean score of fatigue was 8.02 (SD = 3.39). After adjusting for age, gender, marital status, job rank, monthly income, weekly working time, shift and department, EI was negatively associated with fatigue (ß = - 0.270, P <  0.001). SA was positively associated with fatigue (ß = 0.168, P <  0.001), whereas NA was negatively associated with fatigue (ß = - 0.105, P = 0.004); however, DA was not significantly associated with fatigue (ß = 0.034, P = 0.381). Thus, SA (a × b = - 0.026, BCa 95% CI: - 0.050, - 0.011) and NA (a × b = - 0.024, BCa 95% CI: - 0.046, - 0.006) significantly mediated the association between EI and fatigue, respectively. CONCLUSIONS: There was a high level of fatigue among Chinese doctors. EI could indirectly reduce fatigue partially through modifying SA and NA strategies, respectively. EI intervention, education and training in emotional labor should be carried out to cope with fatigue.


Assuntos
Adaptação Psicológica , Inteligência Emocional , Emoções , Fadiga , Processos Mentais , Médicos/psicologia , Autocontrole , Adulto , China , Estudos Transversais , Feminino , Humanos , Masculino , Fadiga Mental , Estresse Ocupacional , Inquéritos e Questionários , Universidades , Trabalho , Adulto Jovem
4.
Mol Biol Evol ; 33(8): 2044-53, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27189569

RESUMO

Nucleotide insertions/deletions are ubiquitous in eukaryotic genomes, and the resulting hemizygous (unpaired) DNA has significant, heritable effects on adjacent DNA. However, little is known about the genetic behavior of insertion DNA. Here, we describe a binary transgenic system to study the behavior of insertion DNA during meiosis. Transgenic Arabidopsis lines were generated to carry two different defective reporter genes on nonhomologous chromosomes, designated as "recipient" and "donor" lines. Double hemizygous plants (harboring unpaired DNA) were produced by crossing between the recipient and the donor, and double homozygous lines (harboring paired DNA) via self-pollination. The transfer of the donor's unmutated sequence to the recipient generated a functional ß-glucuronidase gene, which could be visualized by histochemical staining and corroborated by polymerase chain reaction amplification and sequencing. More than 673 million seedlings were screened, and the results showed that meiotic ectopic recombination in the hemizygous lines occurred at a frequency >6.49-fold higher than that in the homozygous lines. Gene conversion might have been exclusively or predominantly responsible for the gene correction events. The direct measurement of ectopic recombination events provided evidence that an insertion, in the absence of an allelic counterpart, could scan the entire genome for homologous counterparts with which to pair. Furthermore, the unpaired (hemizygous) architectures could accelerate ectopic recombination between itself and interchromosomal counterparts. We suggest that the ectopic recombination accelerated by hemizygous architectures may be a general mechanism for interchromosomal recombination through ubiquitously dispersed repeat sequences in plants, ultimately contributing to genetic renovation and eukaryotic evolution.


Assuntos
Arabidopsis/genética , DNA de Plantas/genética , Mutagênese Insercional , Arabidopsis/metabolismo , Cromossomos , Troca Genética , Conversão Gênica , Hemizigoto , Recombinação Homóloga , Homozigoto , Meiose/genética , Plantas Geneticamente Modificadas , Recombinação Genética , Plântula
5.
Planta ; 246(4): 763-778, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28674753

RESUMO

MAIN CONCLUSION: The contribution of variations in coding regions or promoters to the changes in FAE1 expression levels have be quantified and compared in parallel by specifically designed swapping constructs. FATTY ACID ELONGATION1 (FAE1) is a key gene in control of erucic acid synthesis in plant seeds. The expression of FAE1 genes in Brassica oleracea and Capsella rubella, representatives of high and low erucic acid species, respectively, was characterized to provide insight into the regulation of very long-chain fatty-acid biosynthesis in seeds. Virtually, no methylation was detected either in B. oleracea or in C. rubella, suggesting that modification of promoter methylation might not be a predominant mechanism. Swapping constructs were specifically designed to quantify and compare the contribution of variations in coding regions or promoters to the changes in FAE1 expression levels in parallel. A significantly higher fold change in erucic acid content was observed when swapping coding regions rather than when swapping promoters, indicating that the coding region is a major determinant of the catalytic power of ß-ketoacyl-CoA synthase proteins. Common motifs have been proposed as essential for the preservation of basic gene expression patterns, such as seed-specific expression. However, the occurrence of variation in common cis-elements or the presence of species-specific cis-elements might be plausible mechanisms for changes in the expression levels in different organisms. In addition, conflicting observations in previous reports associated with FAE1 expression are discussed, and we suggest that caution should be taken when selecting a plant transformation vector and in interpreting the results obtained from vectors carrying the CaMV 35S promoter.


Assuntos
Acetiltransferases/metabolismo , Brassica/enzimologia , Capsella/enzimologia , Ácidos Erúcicos/metabolismo , Regulação da Expressão Gênica de Plantas , Acetiltransferases/genética , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Brassica/genética , Capsella/genética , Metilação de DNA , Evolução Molecular , Elongases de Ácidos Graxos , Genes Reporter , Motivos de Nucleotídeos , Fases de Leitura Aberta/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Alinhamento de Sequência , Especificidade da Espécie
6.
Plant Physiol ; 170(4): 2095-109, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26839128

RESUMO

Nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes make up the largest plant disease resistance gene family (R genes), with hundreds of copies occurring in individual angiosperm genomes. However, the expansion history of NBS-LRR genes during angiosperm evolution is largely unknown. By identifying more than 6,000 NBS-LRR genes in 22 representative angiosperms and reconstructing their phylogenies, we present a potential framework of NBS-LRR gene evolution in the angiosperm. Three anciently diverged NBS-LRR classes (TNLs, CNLs, and RNLs) were distinguished with unique exon-intron structures and DNA motif sequences. A total of seven ancient TNL, 14 CNL, and two RNL lineages were discovered in the ancestral angiosperm, from which all current NBS-LRR gene repertoires were evolved. A pattern of gradual expansion during the first 100 million years of evolution of the angiosperm clade was observed for CNLs. TNL numbers remained stable during this period but were eventually deleted in three divergent angiosperm lineages. We inferred that an intense expansion of both TNL and CNL genes started from the Cretaceous-Paleogene boundary. Because dramatic environmental changes and an explosion in fungal diversity occurred during this period, the observed expansions of R genes probably reflect convergent adaptive responses of various angiosperm families. An ancient whole-genome duplication event that occurred in an angiosperm ancestor resulted in two RNL lineages, which were conservatively evolved and acted as scaffold proteins for defense signal transduction. Overall, the reconstructed framework of angiosperm NBS-LRR gene evolution in this study may serve as a fundamental reference for better understanding angiosperm NBS-LRR genes.


Assuntos
Evolução Molecular , Genes de Plantas , Variação Genética , Magnoliopsida/genética , Proteínas NLR/genética , Arabidopsis/genética , Sequência de Bases , Sítios de Ligação , Éxons/genética , Íntrons/genética , Motivos de Nucleotídeos/genética , Filogenia , Especificidade da Espécie
7.
Mol Genet Genomics ; 291(2): 739-52, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26563433

RESUMO

Very long-chain fatty acids (VLCFAs) play an important role in the survival and development of plants, and VLCFA synthesis is regulated by ß-ketoacyl-CoA synthases (KCSs), which catalyze the condensation of an acyl-CoA with malonyl-CoA. Here, we present a genome-wide survey of the genes encoding these enzymes, KCS genes, in 28 species (26 genomes and two transcriptomes), which represents a large phylogenetic scale, and also reconstruct the evolutionary history of this gene family. KCS genes were initially single-copy genes in the green plant lineage; duplication resulted in five ancestral copies in land plants, forming five fundamental monophyletic groups in the phylogenetic tree. Subsequently, KCS genes duplicated to generate 11 genes of angiosperm origin, expanding up to 20-30 members in further-diverged angiosperm species. During this process, tandem duplications had only a small contribution, whereas polyploidy events and large-scale segmental duplications appear to be the main driving force. Accompanying this expansion were variations that led to the sub- and neofunctionalization of different members, resulting in specificity that is likely determined by the 3-D protein structure. Novel functions involved in other physiological processes emerged as well, though redundancy is also observed, largely among recent duplications. Conserved sites and variable sites of KCS proteins are also identified by statistical analysis. The variable sites are likely to be involved in the emergence of product specificity and catalytic power, and conserved sites are possibly responsible for the preservation of fundamental function.


Assuntos
3-Oxoacil-(Proteína de Transporte de Acila) Sintase/genética , Evolução Molecular , Família Multigênica/genética , Filogenia , Sequência de Aminoácidos , Duplicação Gênica , Genoma de Planta , Magnoliopsida/genética , Poliploidia , Transcriptoma/genética
8.
J Integr Plant Biol ; 58(2): 165-77, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25926337

RESUMO

Plant genomes harbor dozens to hundreds of nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes; however, the long-term evolutionary history of these resistance genes has not been fully understood. This study focuses on five Brassicaceae genomes and the Carica papaya genome to explore changes in NBS-LRR genes that have taken place in this Rosid II lineage during the past 72 million years. Various numbers of NBS-LRR genes were identified from Arabidopsis lyrata (198), A. thaliana (165), Brassica rapa (204), Capsella rubella (127), Thellungiella salsuginea (88), and C. papaya (51). In each genome, the identified NBS-LRR genes were found to be unevenly distributed among chromosomes and most of them were clustered together. Phylogenetic analysis revealed that, before and after Brassicaceae speciation events, both toll/interleukin-1 receptor-NBS-LRR (TNL) genes and non-toll/interleukin-1 receptor-NBS-LRR (nTNL) genes exhibited a pattern of first expansion and then contraction, suggesting that both subclasses of NBS-LRR genes were responding to pathogen pressures synchronically. Further, by examining the gain/loss of TNL and nTNL genes at different evolutionary nodes, this study revealed that both events often occurred more drastically in TNL genes. Finally, the phylogeny of nTNL genes suggested that this NBS-LRR subclass is composed of two separate ancient gene types: RPW8-NBS-LRR and Coiled-coil-NBS-LRR.


Assuntos
Brassicaceae/genética , Evolução Molecular , Genes de Plantas , Nucleotídeos/metabolismo , Proteínas de Plantas/genética , Proteínas/genética , Sítios de Ligação , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Duplicação Gênica , Loci Gênicos , Proteínas de Repetições Ricas em Leucina , Funções Verossimilhança , Família Multigênica , Filogenia , Especificidade da Espécie , Sintenia/genética
9.
Plant Physiol ; 166(1): 217-34, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25052854

RESUMO

Proper utilization of plant disease resistance genes requires a good understanding of their short- and long-term evolution. Here we present a comprehensive study of the long-term evolutionary history of nucleotide-binding site (NBS)-leucine-rich repeat (LRR) genes within and beyond the legume family. The small group of NBS-LRR genes with an amino-terminal RESISTANCE TO POWDERY MILDEW8 (RPW8)-like domain (referred to as RNL) was first revealed as a basal clade sister to both coiled-coil-NBS-LRR (CNL) and Toll/Interleukin1 receptor-NBS-LRR (TNL) clades. Using Arabidopsis (Arabidopsis thaliana) as an outgroup, this study explicitly recovered 31 ancestral NBS lineages (two RNL, 21 CNL, and eight TNL) that had existed in the rosid common ancestor and 119 ancestral lineages (nine RNL, 55 CNL, and 55 TNL) that had diverged in the legume common ancestor. It was shown that, during their evolution in the past 54 million years, approximately 94% (112 of 119) of the ancestral legume NBS lineages experienced deletions or significant expansions, while seven original lineages were maintained in a conservative manner. The NBS gene duplication pattern was further examined. The local tandem duplications dominated NBS gene gains in the total number of genes (more than 75%), which was not surprising. However, it was interesting from our study that ectopic duplications had created many novel NBS gene loci in individual legume genomes, which occurred at a significant frequency of 8% to 20% in different legume lineages. Finally, by surveying the legume microRNAs that can potentially regulate NBS genes, we found that the microRNA-NBS gene interaction also exhibited a gain-and-loss pattern during the legume evolution.


Assuntos
Evolução Molecular , Fabaceae/genética , Família Multigênica , Deleção de Genes , Duplicação Gênica , Genoma de Planta , MicroRNAs/metabolismo , Filogenia
10.
Bioorg Med Chem Lett ; 25(22): 5137-41, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26475519

RESUMO

A series of hybrids derived from 4-anilinoquinazoline and hydroxamic acid were designed, synthesized, and evaluated as dual inhibitors of vascular endothelia growth factor receptor-2 (VEGFR-2) tyrosine kinase and histone deacetylase (HDAC). Most of these compounds exhibited potent HDAC inhibition and moderate VEGFR-2 inhibition. Among them, compound 6l exhibited the most potent inhibitory activities against VEGFR-2 (IC50=84 nM) and HDAC (IC50=2.8 nM). It also showed the most potent antiproliferative ability against MCF-7, a human breast cancer line, with IC50 of 1.2 µM. Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction of compound 6l at the active binding sites of VEGFR-2 and HDAC.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Antineoplásicos/síntese química , Domínio Catalítico , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Histona Desacetilases/síntese química , Humanos , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/síntese química , Quinazolinas/síntese química , Relação Estrutura-Atividade
11.
Bioorg Med Chem ; 22(17): 4735-44, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25082515

RESUMO

Both c-Met and VEGFR-2 are important targets for the treatment of cancers. In this study, a series of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinazolin-4-amine derivatives were designed and identified as dual c-Met and VEGFR-2 inhibitors. Among these compounds bearing quinazoline and benzimidazole fragments, compound 7j exhibited the most potent inhibitory activity against c-Met and VEGFR-2 with IC50 of 0.05µM and 0.02µM, respectively. It also showed the highest anticancer activity against the tested cancer cell lines with IC50 of 1.5µM against MCF-7 and 8.7µM against Hep-G2. Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction at the ATP-binding site of c-Met and VEGFR-2, which demonstrates that compound 7j is a potential agent for cancer therapy deserving further researching.


Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/química , Benzimidazóis/farmacologia , Descoberta de Drogas , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Quinazolinas/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Benzimidazóis/síntese química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-met/metabolismo , Quinazolinas/síntese química , Quinazolinas/química , Relação Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
12.
Heliyon ; 10(11): e31990, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38912436

RESUMO

The tourism network attention as a reflection of tourism demand is closely related to the tourism flow, the differences between the two has become an important criterion for judging the efficiency of destination tourism demand conversion, as well as a manifestation of the balance and coordination of destination tourism industry. Against the background of insufficient release of tourism demand in China, research on the development differences between tourism network attention and tourism flow can provide a basis for demand-side management and high-quality development. Based on the theory of spatial mismatch, this research analyzes the spatial development difference between the tourism network attention and the tourism flow in Shanghai from 2012 to 2021 using methods such as center of gravity model, spatial mismatch index, and two-dimensional combination matrix. The results show: (1) According to the analysis of the center of gravity model, there was a shift of the center of gravity of tourism network attention with the direction of "south-north", while the tourism flow shifted "west-east"; the center of gravity between tourism network attention and tourism flow began to diverge from 2012 to 2016, gradually converged from 2016 to 2019, and then gradually deviated again after 2020. (2) According to the spatial mismatch index, the spatial mismatch types between tourism network attention and tourism flow in various Districts of Shanghai are mainly negative and low mismatch, with high mismatch areas mainly distributed in the eastern and southwestern parts of Shanghai. (3) Combining the two-dimensional combination matrix, it can be observed that the spatial development difference between tourism network attention and tourism flow in Shanghai show a characteristic of "enlarging-shrinking-enlarging". From 2012 to 2016, the spatial development difference between tourism network attention and tourism flow in Shanghai continuously expanded; from 2017 to 2019, the spatial development difference continuously shrank; and from 2020 to 2021, the spatial differences expanded again. (4) The analysis results of the panel data model show that the development of tourism resources and the level of tourism services have a positive promoting effect on the evolution of spatial mismatch, while the social basic development environment has a negative effect. The research results not only meet the needs of evaluating the high-quality development of the tourism industry in the current economic restructuring, providing direction for the high-quality development of the regional tourism industry, but also enrich the research content of network attention as a tourism element participating in the evaluation of tourism industry development quality, and deepen the relationship research between network attention and tourism flow.

13.
Chin J Nat Med ; 22(1): 75-88, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38278561

RESUMO

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD+), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.


Assuntos
NAD , Nicotinamida Fosforribosiltransferase , Humanos , NAD/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Citocinas/metabolismo , Quinonas , Oxirredutases
14.
Plant Commun ; 5(1): 100680, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-37660252

RESUMO

Tropane alkaloids (TAs), which are anticholinergic agents, are an essential class of natural compounds, and there is a growing demand for TAs with anesthetic, analgesic, and spasmolytic effects. Anisodus acutangulus (Solanaceae) is a TA-producing plant that was used as an anesthetic in ancient China. In this study, we assembled a high-quality, chromosome-scale genome of A. acutangulus with a contig N50 of 7.4 Mb. A recent whole-genome duplication occurred in A. acutangulus after its divergence from other Solanaceae species, which resulted in the duplication of ADC1 and UGT genes involved in TA biosynthesis. The catalytic activities of H6H enzymes were determined for three Solanaceae plants. On the basis of evolution and co-expressed genes, AaWRKY11 was selected for further analyses, which revealed that its encoded transcription factor promotes TA biosynthesis by activating AaH6H1 expression. These findings provide useful insights into genome evolution related to TA biosynthesis and have potential implications for genetic manipulation of TA-producing plants.


Assuntos
Anestésicos , Solanaceae , Tropanos/análise , Tropanos/metabolismo , Solanaceae/genética , Solanaceae/metabolismo , Cromossomos/química , Cromossomos/metabolismo , Anestésicos/metabolismo , China
15.
Sci China Life Sci ; 67(4): 803-816, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38087029

RESUMO

Living fossils are evidence of long-term sustained ecological success. However, whether living fossils have little molecular changes remains poorly known, particularly in plants. Here, we have introduced a novel method that integrates phylogenomic, comparative genomic, and ecological niche modeling analyses to investigate the rate of molecular evolution of Eupteleaceae, a Cretaceous relict angiosperm family endemic to East Asia. We assembled a high-quality chromosome-level nuclear genome, and the chloroplast and mitochondrial genomes of a member of Eupteleaceae (Euptelea pleiosperma). Our results show that Eupteleaceae is most basal in Ranunculales, the earliest-diverging order in eudicots, and shares an ancient whole-genome duplication event with the other Ranunculales. We document that Eupteleaceae has the slowest rate of molecular changes in the observed angiosperms. The unusually low rate of molecular evolution of Eupteleaceae across all three independent inherited genomes and genes within each of the three genomes is in association with its conserved genome architecture, ancestral woody habit, and conserved niche requirements. Our findings reveal the evolution and adaptation of living fossil plants through large-scale environmental change and also provide new insights into early eudicot diversification.


Assuntos
Evolução Molecular , Magnoliopsida , Filogenia , Ranunculales , Genômica , Magnoliopsida/genética , Ecossistema , Fósseis
16.
Viruses ; 16(5)2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38793554

RESUMO

Monitoring the long-term changes in antibody and cellular immunity following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is crucial for understanding immune mechanisms that prevent reinfection. In March 2023, we recruited 167 participants from the Changning District, Shanghai, China. A subset of 66 participants that were infected between November 2022 and January 2023 was selected for longitudinal follow-up. The study aimed to investigate the dynamics of the immune response, including neutralizing antibodies (NAbs), anti-spike (S)-immunoglobulin G (IgG), anti-S-IgM, and lymphocyte profiles, by analyzing peripheral blood samples collected three to seven months post infection. A gradual decrease in NAbs and IgG levels were observed from three to seven months post infection. No significant differences in NAbs and IgG titers were found across various demographics, including age, sex, occupation, and symptomatic presentation, across five follow-up assessments. Additionally, a strong correlation between NAbs and IgG levels was identified. Lymphocyte profiles showed a slight change at five months but had returned to baseline levels by seven months post infection. Notably, healthcare workers exhibited lower B-cell levels compared to police officers. Our study demonstrated that the immune response to SARS-CoV-2 infection persisted for at least seven months. Similar patterns in the dynamics of antibody responses and cellular immunity were observed throughout this period.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Imunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/epidemiologia , China/epidemiologia , Masculino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Feminino , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Adulto , SARS-CoV-2/imunologia , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Estudos Longitudinais , Imunoglobulina M/sangue , Imunidade Celular , Glicoproteína da Espícula de Coronavírus/imunologia , Pessoal de Saúde
17.
Bioorg Med Chem Lett ; 23(14): 4235-8, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23731945

RESUMO

Two series of thiazole derivatives containing amide skeleton were synthesized and developed as potent Escherichia coli ß-ketoacyl-(acyl-carrier-protein) synthase III (ecKAS III) inhibitors. All the 24 new synthesized compounds were assayed for antibacterial activity against the respective Gram-negative and Gram-positive bacterial strains, including E. coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. In which, 10 compounds with broad-spectrum antibacterial activities were further tested for their ecKAS III inhibitory activity. Last, we have successfully found that compound 4e showed both the promising broad antibacterial activity with MIC of 1.56-6.25µg/mL against the representative bacterial stains, and also processed the most potent ecKAS III inhibitory activity with IC50 of 5.3µM. In addition, docking simulation also carried out in this study to give a potent prediction binding mode between the small molecule and ecKAS III (PDB code: 1hnj) protein.


Assuntos
3-Oxoacil-(Proteína de Transporte de Acila) Sintase/antagonistas & inibidores , Antibacterianos/síntese química , Desenho de Fármacos , Proteínas de Escherichia coli/antagonistas & inibidores , Tiazóis/química , Tiazóis/síntese química , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Sítios de Ligação , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Proteínas de Escherichia coli/metabolismo , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Tiazóis/farmacologia
18.
Asian J Surg ; 46(12): 5507-5508, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37537071

RESUMO

Teachers have applied the "Hand as Foot" teaching method in anatomy teaching. It helps students understand and remember effectively, triggers students' interest in learning, and stimulates creativity. Guided by the teacher, my classmates and I also attempted to design some simple gestures to show the anatomical structures of the bony labyrinth to facilitate memorization. Here, as a medical student, I am glad to share my ideas with you.


Assuntos
Orelha Interna , Estudantes de Medicina , Humanos , Aprendizagem , Mãos ,
19.
Genes (Basel) ; 14(2)2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36833349

RESUMO

A variety of secondary metabolites contributing to plant growth are synthesized by bacterial nonribosomal peptide synthases (NRPSs). Among them, the NRPS biosynthesis of surfactin is regulated by the SrfA operon. To explore the molecular mechanism for the diversity of surfactins produced by bacteria within the genus Bacillus, we performed a genome-wide identification study focused on three critical genes of the SrfA operon-SrfAA, SrfAB and SrfAC-from 999 Bacillus genomes (belonging to 47 species). Gene family clustering indicated the three genes can be divided into 66 orthologous groups (gene families), of which a majority comprised members of multiple genes (e.g., OG0000009 had members of all three SrfAA, SrfAB and SrfAC genes), indicating high sequence similarity among the three genes. Phylogenetic analyses also found that none of the three genes formed monophyletic groups, but were usually arranged in a mixed manner, suggesting the close evolutionary relationship among the three genes. Considering the module structure of the three genes, we propose that self-duplication, especially tandem duplications, might have contributed to the initial establishment of the entire SrfA operon, and further gene fusion and recombination as well as accumulated mutations might have continuously shaped the different functional roles of SrfAA, SrfAB and SrfAC. Overall, this study provides novel insight into metabolic gene clusters and operon evolution in bacteria.


Assuntos
Bacillus , Bacillus subtilis/genética , Filogenia , Peptídeos Cíclicos/genética , Peptídeos Cíclicos/metabolismo , Óperon
20.
Biosensors (Basel) ; 13(6)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37367023

RESUMO

Hydrogen peroxide (H2O2) is one of the important reactive oxygen species (ROS), which is closely related to many pathological and physiological processes in living organisms. Excessive H2O2 can lead to cancer, diabetes, cardiovascular diseases, and other diseases, so it is necessary to detect H2O2 in living cells. Since this work designed a novel fluorescent probe to detect the concentration of H2O2, the H2O2 reaction group arylboric acid was attached to the fluorescein 3-Acetyl-7-hydroxycoumarin as a specific recognition group for the selective detection of hydrogen peroxide. The experimental results show that the probe can effectively detect H2O2 with high selectivity and measure cellular ROS levels. Therefore, this novel fluorescent probe provides a potential monitoring tool for a variety of diseases caused by H2O2 excess.


Assuntos
Corantes Fluorescentes , Peróxido de Hidrogênio , Humanos , Espécies Reativas de Oxigênio , Células HeLa , Fluoresceína
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