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1.
Zool Res ; 45(2): 381-397, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38485507

RESUMEN

The autotetraploid Carassius auratus (4nRR, 4 n=200, RRRR) is derived from whole-genome duplication of Carassius auratus red var. (RCC, 2 n=100, RR). In the current study, we demonstrated that chromatophores and pigment changes directly caused the coloration and variation of 4nRR skin (red in RCC, brownish-yellow in 4nRR). To further explore the molecular mechanisms underlying coloration formation and variation in 4nRR, we performed transcriptome profiling and molecular functional verification in RCC and 4nRR. Results revealed that scarb1, associated with carotenoid metabolism, underwent significant down-regulation in 4nRR. Efficient editing of this candidate pigment gene provided clear evidence of its significant role in RCC coloration. Subsequently, we identified four divergent scarb1 homeologs in 4nRR: two original scarb1 homeologs from RCC and two duplicated ones. Notably, three of these homeologs possessed two highly conserved alleles, exhibiting biased and allele-specific expression in the skin. Remarkably, after precise editing of both the original and duplicated scarb1 homeologs and/or alleles, 4nRR individuals, whether singly or multiply mutated, displayed a transition from brownish-yellow skin to a cyan-gray phenotype. Concurrently, the proportional areas of the cyan-gray regions displayed a gene-dose correlation. These findings illustrate the subfunctionalization of duplicated scarb1, with all scarb1 genes synergistically and equally contributing to the pigmentation of 4nRR. This is the first report concerning the functional differentiation of duplicated homeologs in an autopolyploid fish, substantially enriching our understanding of coloration formation and change within this group of organisms.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Animales , Carpa Dorada/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/veterinaria , Pigmentación/genética , Genoma , Neoplasias Renales/genética , Neoplasias Renales/veterinaria
2.
Front Endocrinol (Lausanne) ; 15: 1336679, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410696

RESUMEN

Introduction: In the Dongting water system, the Carassius auratus (Crucian carp) complex is characterized by the coexistence of diploid forms (2n=100, 2nCC) and polyploidy forms. The diploid (2nCC) and triploid C.auratus (3n=150, 3nCC) had the same fertility levels, reaching sexual maturity at one year. Methods: The nucleotide sequence, gene expression, methylation, and immunofluorescence of the gonadotropin releasing hormone 2(Gnrh2), Gonadotropin hormone beta(Gthß), and Gonadotropin-releasing hormone receptor(Gthr) genes pivotal genes of the hypothalamic-pituitary-gonadal (HPG) axis were analyzed. Results: The analysis results indicated that Gnrh2, follicle-stimulating hormone receptor(Fshr), and Lethal hybrid rescue(Lhr) genes increased the copy number and distinct structural differentiation in 3nCC compared to that in 2nCC. The transcript levels of HPG axis genes in 3nCC were higher than 2nCC (P<0.05), which could promote the production and secretion of sex steroid hormones conducive to the gonadal development of 3nCC. Meanwhile, the DNA methylation levels in the promoter regions of the HPG axis genes were lower in 3nCC than in 2nCC. These results suggested that methylation of the promoter region had a potential regulatory effect on gene expression after triploidization. Immunofluorescence showed that the localization of the Fshß, Lhß, and Fshr genes between 3nCC and 2nCC remained unchanged, ensuring the normal expression of these genes at the corresponding sites after triploidization. Discussion: Relevant research results provide cell and molecular biology evidence for normal reproductive activities such as gonad development and gamete maturation in triploid C. auratus, and contribute to further understanding of the genetic basis for fertility restoration in triploid C. auratus.


Asunto(s)
Carpas , Carpa Dorada , Animales , Carpa Dorada/genética , Triploidía , Eje Hipotálamico-Pituitario-Gonadal , Ploidias , Hormona Liberadora de Gonadotropina/genética
3.
Front Genet ; 14: 1135006, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37056290

RESUMEN

Established autotetraploids often have a highly stable meiosis with high fertility compared with neo-autotetraploids. The autotetraploid Carassius auratus (4n = 200, RRRR) (4nRR), which stemmed from whole-genome duplication of Carassius auratus red var. (2n = 100, RR) (RCC), produces diploid gametes with an adopted diploid-like chromosome pairing in meiosis and maintains the formation of autotetraploid lineages. In this study, we focused on Dmc1, a meiosis-specific recombinase during the prophase of meiosis I, and elaborated on the genetic variation, alternative transcription, expression characterization, and epigenetic modification of Dmc1 in RCC and 4nRR. Two original Dmc1 from RCC were identified in 4nRR, and two duplicated Dmc1 differences in genetic composition were observed in 4nRR. Furthermore, we only noticed that one original and one duplicated Dmc1 were expressed in RCC and 4nRR, respectively. However, both possessed identical gene expression profiles, differential expression of sexual dimorphism, and hypomethylation levels. These results indicated that the specific expression of duplicated Dmc1 may be involve in the progression of meiosis of the diploid-like chromosome pairing in autotetraploid Carassius auratus. Herein, the findings significantly increase knowledge of meiosis of autopolyploid fish and provide meaningful insights into genetic breeding in polyploidy fish.

4.
Water Res ; 233: 119794, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36868113

RESUMEN

Microplastics (MPs) are increasingly released into the environment due to the widespread usage and improper management of plastics. Considerable research efforts have been devoted to the remediation of MPs. Froth flotation has been demonstrated as an effective method to remove MPs in water and sediment. However, there is a lack of knowledge on the regulation of the hydrophobicity/hydrophilicity of MPs surfaces. We found that exposure to the natural environment resulted in the increased hydrophilicity of MPs. The flotation efficiencies of polyvinyl chloride (PVC), polypropylene (PP), polystyrene (PS), and polyethylene glycol terephthalate (PET) MPs decreased to zero after six months of natural incubation in rivers. According to various characterizations, the hydrophilization mechanism is mainly correlated with surface oxidation and the deposition of clay minerals. Inspired by surface wettability conversion, we applied surfactants (collectors) to enhance MPs hydrophobicity and flotation efficiency. Anionic sodium oleate (NaOL) and cationic dodecyl trimethyl ammonium chloride (DTAC) were used to regulate surface hydrophobicity. The effects of collector concentration, pH, conditioning time, and metal ions on MPs flotation were thoroughly elucidated. Characterizations and adsorption experiments were performed to describe the heterogeneous adsorption of surfactants on MPs surfaces. The interaction between surfactants and MPs was explained through density functional theory (DFT) simulations. The dispersion energy between hydrophobic hydrocarbon chains attracts collectors on the MPs surface, and the collector molecules wrap and laminate to MPs surfaces. Flotation using NaOL exhibited a higher removal efficiency, and NaOL was environmentally friendly. Subsequently, we investigated the activation of Ca2+, Fe3+, and Al3+ to further improve the collecting efficiency of NaOL. Under the optimized conditions, MPs in natural rivers could be removed by froth flotation. This study shows the great promise of froth flotation for the application of MPs removal.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Plásticos/química , Poliestirenos , Agua , Tensoactivos
5.
Chemosphere ; 309(Pt 1): 136748, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36209868

RESUMEN

The fight against the COVID-19 epidemic significantly raises the global demand for personal protective equipment, especially disposable face masks (DFMs). The discarded DFMs may become a potential source of microplastics (MPs), which has attracted much attention. In this work, we identified the detailed source of MPs released from DFMs with laser direct infrared spectroscopy. Polypropylene (PP) and polyurethane (PU) accounted for 24.5% and 57.1% of released MPs, respectively. The melt-blown fabric was a dominant MPs source, however, previous studies underestimated the contribution of mask rope. The captured polyethylene terephthalate (PET), polyamide (PA), polyethylene (PE), and polystyrene (PS) in airborne only shared 18.4% of released MPs. To deepen the understanding of MPs release from medical mask into the aquatic environment, we investigated the effects of environmental factors on MPs release. Based on regression analysis, the effects of temperature, incubation time, and wearing time significantly affect the release of MPs. Besides, acidity, alkalinity, sodium chloride, and humic acid also contributed to the MPs release through corroding, swelling, or repulsion of fibers. Based on the exposure of medical mask to simulated environments, the number of released MPs followed the order: seawater > simulated gut-fluid > freshwater > pure water. Considering the risk of MPs released from DFMs to the environment, we innovatively established a novel flotation removal system combined with cocoamidopropyl betaine, achieving 86% removal efficiency of MPs in water. This work shed the light on the MPs release from DFMs and proposed a removal strategy for the control of MPs pollution.


Asunto(s)
COVID-19 , Contaminantes Químicos del Agua , Humanos , Microplásticos , Plásticos , Poliestirenos/química , Polipropilenos , Tereftalatos Polietilenos , Sustancias Húmicas , Máscaras , Nylons , Poliuretanos , Cloruro de Sodio , Betaína , Contaminantes Químicos del Agua/análisis , Polietileno/química , Agua
6.
Chemosphere ; 303(Pt 2): 135123, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35643161

RESUMEN

Nano zero-valent iron loaded porous carbon derived from microplastics was designed as heterogeneous catalyst for degradation of persistent organic pollutants. Controlled carbonization of microplastics with molten salt was conducted to tune the morphology of carbon product. Controlled carbonization induces higher carbon yield (from 17.73% to 52.24%) and larger surface area (from 403.72 m2/g to 601.82 m2/g). The catalyst (Fe/MMPC) was characterized by Raman, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscope. Loading nano zero-valent iron onto porous carbon are verified in the catalyst. The process factors including Fe/MMPC dosage, H2O2, pH, anions, and temperature were studied to estimate the catalytic performance. Tetracycline degradation (81.8% within 10 min) is effectively obtained in the Fe/MMPC and H2O2 system. The apparent rate constant is 0.1311-0.2999 min-1 under different temperature, and the activation energy of catalytic process is 22 kJ/mol. Pollutants including rhodamine B, p-nitrophenol, and butylxanthate are efficiently degraded in the catalytic system. The predominant species of catalytic reactions are hydroxyl radicals, which are mainly produced from H2O2 activation enhanced by zero-valent iron in Fe/MMPC. This work offers an innovative strategy for microplastic management and wastewater treatment.


Asunto(s)
Hierro , Contaminantes Químicos del Agua , Antibacterianos/química , Carbono , Peróxido de Hidrógeno/química , Hierro/química , Microplásticos , Plásticos , Tetraciclina , Contaminantes Químicos del Agua/análisis
7.
Waste Manag ; 149: 1-10, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35689973

RESUMEN

The mismanagement of waste electrical and electronic equipment (WEEE) resulted in numerous discarded plastics in the natural environment, and these waste plastics might experience aging, breaking, and migration, which becomes a crucial microplastic source. Sustainable management of WEEE plastics presents a considerable opportunity for resource recovery and microplastic pollution prevention. Flotation separation is a significant process of mechanical recycling, while most flotation methods can only deal with binary plastic mixtures. In this work, an advanced, stepwise, and sustainable flotation method was advocated to separate multi-plastics by polymeric aluminum chloride (PAC) modification. The abundant hydrophilic groups and environmental friendliness of PAC prompted us to further investigate the wetting effect. PAC had varied hydrophilization effects on acrylonitrile butadiene styrene (ABS) and polystyrene (PS) surfaces, but polyethylene terephthalate (PET) retained hydrophobicity. Treatment conditions, including PAC dosage, temperature, time, and pH were optimized. 100% of PET could be purified after primary separation, and the purities of ABS and PS could reach 100% and 97.4% after secondary separation, respectively. The strength of the interaction was determined by the different surface potentials and functional groups. In PAC solution, long-chain molecules or ions might interact with plastic surfaces electrostatically, and Al3+ could bridge long-chain molecules and plastic surfaces, thereby strengthening the polymer hydrophilicity. We further improved the PAC treatment process, and the reuse of PAC reduced modifier usage to 84.4 g/ton waste plastics, which was cost-effective in industrial applications. A preliminary evaluation of the energy consumption and environmental impact indicated that PAC treatment was superior to other modification methods. This work is an initial attempt at the stepwise separation of waste plastic and shows promising prospects for recycling plastic waste.


Asunto(s)
Acrilonitrilo , Eliminación de Residuos , Acrilonitrilo/química , Cloruro de Aluminio , Electrónica , Microplásticos , Plásticos/química , Tereftalatos Polietilenos , Polímeros/química , Poliestirenos/química , Reciclaje , Eliminación de Residuos/métodos
8.
BMC Ecol Evol ; 21(1): 201, 2021 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-34740327

RESUMEN

BACKGROUND: Autotetraploid Carassius auratus (4n = 200, RRRR) (abbreviated as 4nRR) is derived from whole genome duplication of Carassius auratus red var. (2n = 100, RR) (abbreviated as RCC). Ribosome DNA (rDNA) is often used to study molecular evolution of repeated sequences because it has high copy number and special conserved coding regions in genomes. In this study, we analysed the sequences (5S, ITS1-5.8S-ITS2 region), structure, methylation level (NTS and IGS), and expression level (5S and 18S) of 5S and 45S ribosomal RNA (rRNA) genes in 4nRR and RCC in order to elucidate the effects of autotetraploidization on rDNA in fish. RESULTS: Results showed that there was high sequence similarity of 5S, 5.8S and ITS1 region between 4nRR and RCC. This study also identified two different types of ITS2 region in 4nRR and predicted the secondary structure of ITS2. It turns out that both secondary structures are functional. Compared with RCC, there was no significant difference in NTS (5S rRNA) methylation level, but the expression level of 5S rRNA was lower in 4nRR, indicating that methylation had little effect on the expression level in 4nRR. IGS (45S rRNA) was hypermethylated in 4nRR compared to RCC, but the expression of 18S rRNA gene was no significantly different from that in RCC, indicating that methylation regulation affected gene expression in 4nRR. CONCLUSION: The above studies initially revealed the effects of autotetraploidization on the structure and function of 5S and 45S rRNA in Carassius auratus, and provided a theoretical support for the systematic study of the evolution pattern and characteristics of rDNA in vertebrates.


Asunto(s)
Carpa Dorada , ARN Ribosómico 5S , Animales , ADN Ribosómico , Evolución Molecular , Carpa Dorada/genética , ARN Ribosómico 18S
9.
J Environ Manage ; 299: 113626, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34488105

RESUMEN

Polyvinyl chloride (PVC) and polycarbonate (PC) microplastics are major sources of hazardous chlorine and bisphenol A, threatening the ecosystem and environment. Plastic recycling can control the source of microplastics pollution, but the recycling of PVC and PC will be prevented by invalid separation. We established a novel and clean flotation method to separate PVC and PC microplastics by using aluminum coating. Trace amounts of Al(OH)3 can selectively coat the PVC microplastics surface due to its strong affinity for PVC. The contact angle of PVC decreases by 24° due to abundant hydroxyl groups of Al(OH)3 coating, whereas PC remained hydrophobic. Response surface methodology (RSM) combining Box-Behnken design (BBD) is used to optimize modification. A quadratic model is established to predict PC purity, explore the interaction between pH, aluminum chloride concentration, and ultrasonic duration. The recovery and purity of microplastics can exceed 99.65% with parameter optimization. The effects of multi-component, brand, shape, size, and mass ratio of plastics are utilized to evaluate the application potential. The suitable situations and limits of this method are disclosed. The aluminum coating offers significant benefits over other modifications in terms of reaction temperature, treatment time, and pollution prevention. Flotation based on aluminum coating provides a new insight for separating and recycling microplastics.


Asunto(s)
Cloruro de Polivinilo , Eliminación de Residuos , Aluminio , Ecosistema , Microplásticos , Plásticos , Cemento de Policarboxilato
10.
Science ; 373(6552): 315-320, 2021 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-34437149

RESUMEN

The development of low-cost, efficient physisorbents is essential for gas adsorption and separation; however, the intrinsic tradeoff between capacity and selectivity, as well as the unavoidable shaping procedures of conventional powder sorbents, greatly limits their practical separation efficiency. Herein, an exceedingly stable iron-containing mordenite zeolite monolith with a pore system of precisely narrowed microchannels was self-assembled using a one-pot template- and binder-free process. Iron-containing mordenite monoliths that could be used directly for industrial application afforded record-high volumetric carbon dioxide uptakes (293 and 219 cubic centimeters of carbon dioxide per cubic centimeter of material at 273 and 298 K, respectively, at 1 bar pressure); excellent size-exclusive molecular sieving of carbon dioxide over argon, nitrogen, and methane; stable recyclability; and good moisture resistance capability. Column breakthrough experiments and process simulation further visualized the high separation efficiency.

11.
Waste Manag ; 118: 471-480, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32979778

RESUMEN

Waste polystyrene (PS) and polycarbonate (PC) are crucial components arising from mixtures of plastic products, whose recycling is significantly limited by separation efficiency. In this work, to assist the flotation separation of PC and PS, we proposed a novel modification technology of surface alkoxylation pretreatment (SAP) where PC surface reacted with glycerol and urea. The SAP could selectively transform the hydrophobic PC into hydrophilic plastic, while the PS remained its hydrophobic surface owing to the exclusion from SAP process. Benefiting from the hydrophilic PC, the separation efficiency of PS and PC could reach the maximum of 99.34% under optimum conditions (urea dosage of 5 g, pretreatment temperature of 130 °C, pretreatment time of 10 min, flotation time of 2.5 min, frother concentration of 16.5 mg/L, and airflow rate of 7.2 mL/min). The mechanism of SAP was systematically analyzed by wettability, surface morphology, molecular weight, and chemical reactions. Compared with PS plastic, the pretreated PC presented better wettability, rougher surface, and significantly reducing molecular weight. The improvement of PC hydrophilicity can be attributed to the cleavage of ester bonds on backbone chains and the introduction of hydrophilic hydroxyl groups. The effective SAP process proves that chemical recycling of waste plastic can provide a novel strategy for surface modification and flotation separation of PS and PC.


Asunto(s)
Poliestirenos , Eliminación de Residuos , Interacciones Hidrofóbicas e Hidrofílicas , Plásticos , Cemento de Policarboxilato
12.
BMC Genet ; 21(1): 35, 2020 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-32199463

RESUMEN

BACKGROUND: Autotetraploid Carassius auratus (4nRCC, 4n = 200, RRRR) was derived from the whole genome duplication of diploid red crucian carp (Carassius auratus red var.) (2nRCC, 2n = 100, RR). To investigate the genetic effects of tetraploidization, we analyzed DNA variation, epigenetic modification and gene expression changes in the Sox9a-Amh-Cyp19a1a regulatory cascade between 4nRCC and 2nRCC. RESULTS: We found that the Sox9a gene contained two variants in 2nRCC and four variants in 4nRCC. Compared with that in 2nRCC, DNA methylation in the promoter regions of the Amh and Cyp19a1a genes in 4nRCC was altered by single nucleotide polymorphism (SNP) mutations, which resulted in the insertions and deletions of CpG sites, and the methylation levels of the Sox9a, Amh and Cyp19a1a genes increased after tetraploidization. The gene expression level of the Sox9a-Amh-Cyp19a1a regulatory cascade was downregulated in 4nRCC compared with that in 2nRCC. CONCLUSION: The above results demonstrate that tetraploidization leads to significant changes in the genome, epigenetic modification and gene expression in the Sox9a-Amh-Cyp19a1a regulatory cascade; these findings increase the extant knowledge regarding the effects of polyploidization.


Asunto(s)
Aromatasa/genética , Carpa Dorada/genética , Receptores de Péptidos/genética , Receptores de Factores de Crecimiento Transformadores beta/genética , Factor de Transcripción SOX9/genética , Animales , Diploidia , Genoma/genética , Carpa Dorada/crecimiento & desarrollo , Tetraploidía , Proteínas de Pez Cebra
13.
Gene ; 737: 144433, 2020 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-32014563

RESUMEN

The Carassius auratus (crucian carp) complex of the Dongting water system exhibits coexistence of diploid and triploid forms. As reported, triploid C. auratus is autotriploid origin. Ribosomal DNA (rDNA) with evolutionary conservation is widely used to study polyploidization. Here, we investigated genomic and transcribed rDNA sequences (18S and 5S) in diploid (2nCC, 2n = 100) and triploid (3nCC, 3n = 150) C. auratus. The results showed that the genetic traits and expression of 18S and 5S rDNA from 2nCC individuals were identified in 3nCC individuals. Moreover, pseudogenization of rDNA (18S and 5S) sequences were also observed in both 2nCC and 3nCC individuals, but expression of these variants was not detected. Based on the transcribed rDNA consensus sequence between 2nCC and 3nCC individuals, the functional secondary structures of 18S rRNA (expansion segments, ES6S) and 5S rRNA were predicted. These data demonstrated that complex evolutionary dynamics existed in the rDNA family of C. auratus. The evolutionary conservation of rDNA revealed that autotriploidization could not induce the divergence in Carassius taxa of the Dongting water system. These observations will expand our knowledge of the evolutionary dynamics of the rDNA family in vertebrates.


Asunto(s)
ADN Ribosómico/genética , Carpa Dorada/genética , ARN Ribosómico 18S/genética , ARN Ribosómico 5S/genética , Triploidía , Animales , Secuencia de Bases , ADN Ribosómico/química , Evolución Molecular , Carpa Dorada/clasificación , Conformación de Ácido Nucleico , Filogenia , ARN Ribosómico 18S/química , ARN Ribosómico 5S/química , Alineación de Secuencia
14.
Front Genet ; 11: 576260, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33488668

RESUMEN

Whole genome duplication events have occurred frequently during the course of vertebrate evolution. To better understand the influence of polyploidization on the fish genome, we herein used the autotetraploid Carassius auratus (4n = 200, RRRR) (4nRR) resulting from the whole genome duplication of Carassius auratus (2n = 100, RR) (RCC) to explore the genomic and epigenetic alterations after polyploidization. We subsequently performed analyses of full-length transcriptome dataset, amplified fragment length polymorphism (AFLP) and methylation sensitive amplification polymorphism (MSAP) on 4nRR and RCC. By matching the results of 4nRR and RCC isoforms with reference genome in full-length transcriptome dataset, 649 and 1,971 novel genes were found in the RCC and 4nRR full-length geneset, respectively. Compared to Carassius auratus and Megalobrama amblycephala, 4nRR presented 3,661 unexpressed genes and 2,743 expressed genes. Furthermore, GO enrichment analysis of expressed genes in 4nRR revealed that they were enriched in meiosis I, whereas KEGG enrichment analysis displayed that they were mainly enriched in proteasome. Using AFLP analysis, we noted that 32.61% of RCC fragments had disappeared, while 32.79% of new bands were uncovered in 4nRR. Concerning DNA methylation, 4nRR exhibited a lower level of global DNA methylation than RCC. Additionally, 60.31% of methylation patterns in 4nRR were altered compared to RCC. These observations indicated that transcriptome alterations, genomic changes and regulation of DNA methylation levels and patterns had occurred in the newly established autotetraploid genomes, suggesting that genetic and epigenetic alterations were influenced by autotetraploidization. In summary, this study provides valuable novel insights into vertebrate genome evolution and generates relevant information for fish breeding.

15.
Eur J Med Chem ; 177: 448-456, 2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31174062

RESUMEN

The colchicine site inhibitors (CSIs) showed promising prospects as antitumor agents due to their vascular disrupting activities besides antimitotic activities. 1-Phenyl-dihydrobenzoindazole was found as a novel scaffold of CSI without the cis-trans isomerization problem. The X-ray co-crystal structure of the lead compound with tubulin was determined, which revealed the binding mode including special water-bridged hydrogen bonds. The structure also provided guidance for the structural optimization of this type of CSI, which led to the discovery of the most potent inhibitor A3, with growth IC50 lower than 1 nM against human colon cancer cell lines and tubulin polymerization IC50 of 1.6 µM. In addition, its water-soluble prodrug B1 showed good in vivo antitumor activity on two human colon cancer xenograft nude mice models, encouraging further study of this type of antitumor compound.


Asunto(s)
Antineoplásicos/farmacología , Sitios de Unión/efectos de los fármacos , Indazoles/farmacología , Moduladores de Tubulina/farmacología , Tubulina (Proteína)/metabolismo , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/metabolismo , Femenino , Células HCT116 , Humanos , Indazoles/síntesis química , Indazoles/química , Indazoles/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Estructura Molecular , Profármacos/síntesis química , Profármacos/química , Profármacos/metabolismo , Profármacos/farmacología , Unión Proteica/efectos de los fármacos , Solubilidad , Tubulina (Proteína)/química , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química , Moduladores de Tubulina/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Front Genet ; 10: 437, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31156700

RESUMEN

The autotetraploid fish (4n = 200, RRRR) (abbreviated as 4nRR) resulted from the whole genome duplication of red crucian carp (Carassius auratus red var., 2n = 100, RR) (abbreviated as RCC). During investigation of the influence of polyploidization on organization and evolution of the multigene family of 5S rDNA, molecular organization and chromosomal localization of the 5S rDNA were characterized in autotetraploid fish. By sequence analysis of the coding region (5S) and adjacent non-transcribed spacer (NTS), three distinct 5S rDNA units (type I: 203 bp; type II: 340 bp; and type III: 477bp) were identified and characterized in 4nRR. These 5S rDNA units were inherited from their female parent (RCC), in which obvious base variations in NTS and array recombination of repeat units were found. Using fluorescence in situ hybridization employing different 5S rDNA units as probes, these 5S rDNA clusters were localized in chromosomes of 4nRR, respectively, and showed obvious loss of chromosomal loci (type I and type II). Our data revealed genetic variation of the 5S rDNA multigene family in the genome of autopolyploid fish. Furthermore, results provided new insights into the evolutionary patterns of this vertebrate multigene family.

17.
BMC Genomics ; 20(1): 306, 2019 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-31014252

RESUMEN

BACKGROUND: DNA methylation plays an important role in multiple biological processes that are closely related to human health. The study of DNA methylation can provide an insight into the mechanism behind human health and can also have a positive effect on the assessment of human health status. However, the available sequencing technology is limited by incomplete CpG coverage. Therefore, it is crucial to discover an efficient and convenient method capable of distinguishing between the states of CpG sites. Previous studies focused on identifying methylation states of the CpG sites in single cell, which only evaluated sequence information or structural information. RESULTS: In this paper, we propose a novel model, LightCpG, which combines the positional features with the sequence and structural features to provide information on the CpG sites at two stages. Next, we used the LightGBM model for training of the CpG site identification, and further utilized sample extraction and merged features to reduce the training time. Our results indicate that our method achieves outstanding performance in recognition of DNA methylation. The average AUC values of our method using the 25 human hepatocellular carcinoma cells (HCC) cell datasets and six human heptoplastoma-derived (HepG2) cell datasets were 0.9616 and 0.9213, respectively. Moreover, the average training times for our method on the HCC and HepG2 datasets were 8.3 and 5.06 s, respectively. Furthermore, the computational complexity of our model was much lower compared with other available methods that detect methylation states of the CpG sites. CONCLUSIONS: In summary, LightCpG is an accurate model for identifying the DNA methylation status of CpG sites in single cells. Furthermore, three types of feature extraction methods and two strategies used in LightCpG are helpful for other prediction problems.


Asunto(s)
Islas de CpG/genética , Análisis de la Célula Individual , Secuenciación Completa del Genoma , Carcinoma Hepatocelular/patología , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología
18.
Front Genet ; 10: 208, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30941161

RESUMEN

Polyploidization can significantly alter the size of animal gametes. Autotetraploid fish (RRRR, 4nRR = 200) (4nRR) possessing four sets of chromosomes were derived from whole-genome duplication in red crucian carp (RR, 2n = 100) (RCC). The diploid eggs of the 4nRR fish were significantly larger than the eggs of RCC. To explore the differences between the ovaries of these two ploidies of fishes at the molecular level, we compared the ovary transcriptome profiles of 4nRR fish and RCC and identified differentially expressed genes (DEGs). A total of 19,015 unigenes were differentially expressed between 4nRR fish and RCC, including 12,591 upregulated and 6,424 downregulated unigenes in 4nRR fish. Functional analyses revealed that eight genes (CDKL1, AHCY, ARHGEF3, TGFß, WNT11, CYP27A, GDF7, and CKB) were involved in the regulation of cell proliferation, cell division, gene transcription, ovary development and energy metabolism, suggesting that these eight genes were related to egg size in 4nRR fish and RCC. We validated the expression levels of these eight DEGs in 4nRR fish and RCC using quantitative PCR. The study results provided insights into the regulatory mechanisms underlying the differences in crucian carp egg sizes.

19.
Bioorg Med Chem Lett ; 29(3): 349-352, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30594434

RESUMEN

Multiple myeloma (MM) is the second most common haematological malignancy. Almost all patients with MM eventually relapse, and most recommended treatment protocols for the patients with relapsed refractory MM comprise a combination of drugs with different mechanisms of action. Therefore novel drugs are in urgent need in clinic. Bcl-2 inhibitors and HDAC inhibitors were proved their anti-MM effect in clinic or under clinical trials, and they were further discovered to have synergistic interactions. In this study, a series of Bcl-2/HDAC dual-target inhibitors were designed and synthesized. Among them, compounds 7e-7g showed good inhibitory activities against HDAC6 and high binding affinities to Bcl-2 protein simultaneously. They also displayed good growth inhibitory activities against human MM cell line RPMI-8226, which proved their potential value for the treatment of multiple myeloma.


Asunto(s)
Antineoplásicos/farmacología , Diseño de Fármacos , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Mieloma Múltiple/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/química , Humanos , Modelos Moleculares , Estructura Molecular , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Relación Estructura-Actividad
20.
Waste Manag ; 78: 829-840, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32559978

RESUMEN

This work develops a simple and practical process for separation of acrylonitrile-butadienestyrene (ABS) and polystyrene (PS) waste plastics by froth flotation after surface modification using potassium ferrate. ABS plastics containing brominated flame retardants (BFRs) can release hazardous emissions during the process of disposal. Moreover, ABS and PS are typical styrene plastics with similar properties, posing severe restrictions on their separation for recycling. Thus, potassium ferrate modification was investigated and found to decrease selectively the floatability of ABS, providing available process for separation of ABS and PS. Contact angle measurements, FT-IR, XPS and SEM characterization analysis confirmed that potassium ferrate modification can induce the desired changes in the surface properties of ABS. With consideration to separation of ABS and PS, the optimum conditions are potassium ferrate concentration 0.15 M/L, modification time 15 min, temperature 60 °C, stirring rate 200 rpm, frother concentration 14.50 mg/L and flotation time 2 min. Under optimum conditions, separation of ABS and PS with different mixing ratios was accomplished with a recovery and purity of 98.60% and 98.62% respectively. Moreover, reusing of potassium ferrate solution is feasible, further eliminating emissions and cost of this process. Consequently, surface modification using potassium ferrate can be applied for facilitating flotation separation of ABS and PS waste plastics.

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