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1.
Artigo em Inglês | MEDLINE | ID: mdl-38358866

RESUMO

Implicit neural representation (INR) characterizes the attributes of a signal as a function of corresponding coordinates which emerges as a sharp weapon for solving inverse problems. However, the expressive power of INR is limited by the spectral bias in the network training. In this paper, we find that such a frequency-related problem could be greatly solved by re-arranging the coordinates of the input signal, for which we propose the disorder-invariant implicit neural representation (DINER) by augmenting a hash-table to a traditional INR backbone. Given discrete signals sharing the same histogram of attributes and different arrangement orders, the hash-table could project the coordinates into the same distribution for which the mapped signal can be better modeled using the subsequent INR network, leading to significantly alleviated spectral bias. Furthermore, the expressive power of the DINER is determined by the width of the hash-table. Different width corresponds to different geometrical elements in the attribute space, e.g., 1D curve, 2D curved-plane and 3D curved-volume when the width is set as 1, 2 and 3, respectively. More covered areas of the geometrical elements result in stronger expressive power. Experiments not only reveal the generalization of the DINER for different INR backbones (MLP vs. SIREN) and various tasks (image/video representation, phase retrieval, refractive index recovery, and neural radiance field optimization) but also show the superiority over the state-of-the-art algorithms both in quality and speed. Project page: https://ezio77.github.io/DINER-website/.

2.
J Youth Adolesc ; 53(5): 1091-1100, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38097884

RESUMO

Perceived parental expectations of adolescents have been linked to many high school consequences, yet few studies have examined the relationship between perceived parental expectations and adolescents' career aspirations, and potential mechanisms that underlie these associations. To address this research gap, this study investigated the reciprocal relationship between perceived parental expectations and career aspirations, as well as the mediating role of adolescents' career exploration among Chinese adolescents. Using a longitudinal design, a total of 2540 senior high school students (51.38% girls, Mage = 17.09 ± 0.69) participated in the study. The results showed that perceived parental expectations of adolescents have no direct impact on their subsequent career aspirations. A longitudinal mediating role of career exploration was found between perceived parental expectations and career aspirations. No gender differences were found in any of the pathways. These findings provided support for helping adolescents better set their career aspirations by acknowledging the critical role of parental expectations and the mediating role of career exploration.


Assuntos
Motivação , Pais , Feminino , Humanos , Adolescente , Masculino , Escolaridade , Estudantes , Instituições Acadêmicas
3.
J Med Chem ; 66(16): 10917-10933, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37535706

RESUMO

Targeted protein degradation (TPD) technologies have catalyzed a paradigm shift in therapeutic strategies and offer innovative avenues for drug design. Hydrophobic tags (HyTs) are bifunctional TPD molecules consisting of a ″lipophilic small-molecule tags″ group and a small-molecule ligand for the target protein. Despite the vast potential of HyTs, they have received relatively limited attention as a promising frontier. Leveraging their lower molecular weight and reduced numbers of hydrogen bond donors/acceptors (HBDs/HBAs) in comparison with proteolysis-targeting chimeras (PROTACs), HyTs present a compelling approach for enhancing druglike properties. In this Perspective, we explore the diverse range of HyT structures and their corresponding degradation mechanisms, thereby illuminating their broad applicability in targeting a diverse array of proteins, including previously elusive targets. Moreover, we scrutinize the challenges and opportunities entailed in developing this technology as a viable and fruitful strategy for drug discovery.


Assuntos
Descoberta de Drogas , Proteínas , Proteólise , Proteínas/metabolismo , Desenho de Fármacos , Ubiquitinação , Ubiquitina-Proteína Ligases/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo
4.
Eur J Med Chem ; 253: 115338, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37037138

RESUMO

Currently, bioorthogonal coupling reactions have garnered considerable interest due to their high substrate selectivity and less restrictive reaction conditions. During recent decades, bioorthogonal coupling reactions have emerged as powerful tools in drug development. This review describes the current applications of bioorthogonal coupling reactions in compound library building mediated by the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and in situ click chemistry or conjunction with other techniques; druggability optimization with 1,2,3-triazole groups; and intracellular self-assembly platforms with ring tension reactions, which are presented from the viewpoint of drug development. There is a reasonable prospect that bioorthogonal coupling reactions will accelerate the screening of lead compounds, the designing strategies of small molecules and expand the variety of designed compounds, which will be a new trend in drug development in the future.


Assuntos
Cobre , Desenvolvimento de Medicamentos , Cobre/química , Reação de Cicloadição , Azidas/química , Química Click/métodos , Alcinos/química , Catálise
5.
Angew Chem Int Ed Engl ; 62(13): e202217246, 2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670545

RESUMO

Hydrophobic tagging (HyT) is a potential therapeutic strategy for targeted protein degradation (TPD). Norbornene was discovered as an unprecedented hydrophobic tag in this study and was used to degrade the anaplastic lymphoma kinase (ALK) fusion protein by linking it to ALK inhibitors. The most promising degrader, Hyt-9, potently reduced ALK levels through Hsp70 and the ubiquitin-proteasome system (UPS) in vitro without compensatory upregulation of ALK. Furthermore, Hyt-9 exhibited a significant tumor-inhibiting effect in vivo with moderate oral bioavailability. More importantly, norbornene can also be used to degrade the intractable enhancer of zeste homolog 2 (EZH2) when tagged with the EZH2 inhibitor tazemetostat. Thus, the discovery of novel hydrophobic norbornene tags shows promise for the future development of TPD technology.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Proteólise , Inibidores Enzimáticos , Complexo de Endopeptidases do Proteassoma , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/química
6.
Bioorg Chem ; 131: 106327, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36549254

RESUMO

Protopanoxadiol is a key active ingredient derived from Panax ginseng that is well-known to exhibit anti-tumor activity. Previous research focused on the natural protopanaxadiol derivative AD-1 has demonstrated that it possesses broad spectrum anti-tumor activities in vitro and in vivo. However, its limited activity, selectivity, and cell permeability have impeded its therapeutic application. Herein, a series of novel AD-1 derivatives were designed and synthesized based on proteolysis-targeting chimera (PROTAC) technology by linking AD-1 at the C-3 and C-12 positions with pomalidomide through linkers of alkyl chain of differing lengths to achieve the goal of improving the efficacy of the parent compound. Among these synthesized PROTACs, the representative compound A05 exhibited the most potent anti-proliferative activity against A549 cells. Furthermore, mechanistic studies revealed that compound A05 was able to suppress MDM2 expression, disrupt interactions between p53 and MDM2 and readily induce apoptotic death via the mitochondrial apoptosis pathway. Moreover, the in vivo assays revealed that compound A05 exhibited both anti-proliferative and anti-metastatic activities in the zebrafish tumor xenograft model with A549 cells. Together, our findings suggest that AD-1 based PROTACs associated with the degradation of MDM2 may have promising effects for the treatment of lung cancer and this work provide a foundation for future efforts to develop novel anti-tumor agents from natural products.


Assuntos
Antineoplásicos , Desenho de Fármacos , Neoplasias Pulmonares , Quimera de Direcionamento de Proteólise , Animais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Proliferação de Células , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proteólise , Quimera de Direcionamento de Proteólise/síntese química , Quimera de Direcionamento de Proteólise/química , Quimera de Direcionamento de Proteólise/farmacologia , Peixe-Zebra , Células A549
7.
Environ Sci Pollut Res Int ; 30(2): 4959-4971, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35976583

RESUMO

Mining activities can result in severe heavy metal contamination in freshwater ecosystems and lead to significant health risks. In this study, eight heavy metal concentrations in the water, sediments and aquatic organisms, including eighteen fish species, two shrimp species, one crab species and one amphibian frog species of the abandoned Shimen Realgar Mine area, were analysed. The results showed that most of the heavy metals detected in water, sediments and fish from the mine area were at relatively high levels, and historical realgar mining activities were a major source of arsenic (As) contamination in this area. We concluded that heavy metal bioaccumulation is species- and tissue-specific and is different for each element and sampling site. The concentration of heavy metals in fish was generally lower than that of the other aquatic organism species; these concentrations varied among different species with different feeding habits and habitats. The study showed that heavy metal concentrations were lower in muscle tissue than in other tissues (e.g. liver, skin, exoskeleton). A significant positive correlation between the As concentrations in sediment and fish was observed, indicating that sediment is an important factor affecting As accumulation in fish; thus, for fish protection, controlling the sources of water and sediment contamination is essential. Furthermore, the estimated daily intake (EDI) of all metals was acceptable, and the corresponding target hazard quotient (THQ) and total target hazard quotient (TTHQ) values were less than 1; hence, there was no serious health risk through fish consumption in this area.


Assuntos
Arsênio , Metais Pesados , Poluentes Químicos da Água , Animais , Organismos Aquáticos , Água/análise , Ecossistema , Monitoramento Ambiental/métodos , Metais Pesados/análise , Arsênio/análise , Peixes , Poluentes Químicos da Água/análise , Medição de Risco , Sedimentos Geológicos
8.
Artigo em Inglês | MEDLINE | ID: mdl-36360697

RESUMO

Pb and Cd accumulation in riparian soils and river sediments in river basins is a challenging pollution issue due to the persistence and bioaccumulation of these two trace metals. Understanding the migration characteristics and input sources of these metals is the key to preventing metal pollution. This study was conducted to explore the contents, geochemical fractionation, and input sources of Pb and Cd in riparian soils and river sediments from three lower reaches of the Pearl River Delta located in the Guangdong-Hong Kong-Macao Greater Bay Area. The total concentration of all Pb and Cd values exceeded the background values to varying degrees, and the exchangeable fraction of Cd in riparian soils and river sediments accounted for the largest proportion, while that of Pb was dominated by the residual fraction. Geoaccumulation index calculations showed that in the riparian soils, the average accumulation degree of Pb (0.52) in the Beijiang River (BJR) was the highest, while that of Cd (2.04) in the Xijiang River (XJR) was the highest. Unlike that in riparian soils, the maximum accumulation of Pb (0.76) and Cd (3.01) in river sediments both occurred in the BJR. Furthermore, the enrichment factor results also showed that Pb and Cd in the riparian soils and river sediments along the BJR were higher than those in the XJR and Dongjiang River (DJR). The relationship between enrichment factors and nonresidual fractions further proved that the enrichment factors of Cd were significantly correlated with the nonresidual fractions of Cd, which may imply various anthropogenic sources of Cd in the three reaches. Moreover, source identification based on principal component analysis (PCA) and Pb isotope ratio analysis indicated that riparian soils and river sediments have inconsistent pollution source structures. The PCA results showed that Pb and Cd were homologous inputs in the DJR, and there were significant differences only in the riparian soils and river sediments. Pb isotope tracing results further showed that the bedrock of high geological background from upstream may be the main reason for Cd accumulation in the XJR. However, the ultrahigh accumulation of Cd in the BJR is mainly caused by the input of the upstream mining and metallurgy industry. The control of upstream input sources will be the key to the prevention of trace metal pollution in these regions.


Assuntos
Metais Pesados , Oligoelementos , Poluentes Químicos da Água , Rios/química , Solo/química , Metais Pesados/análise , Cádmio/análise , Chumbo/análise , Sedimentos Geológicos/química , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Medição de Risco/métodos , Oligoelementos/análise , China
9.
Artigo em Inglês | MEDLINE | ID: mdl-35564638

RESUMO

Tea is the main commercial crop grown in China, and excessive application of chemical fertilizers in tea plantations is common. However, the potential to reduce chemical fertilizer use in tea plantations is unclear. In this study, Zhejiang Province was selected as the research object to systematically analyze the potential for tea plantation chemical-fertilizer reduction at different spatial scales. The geographic information system-based analytic hierarchy process method and Soil and Water Assessment Tool model were used to determine the chemical fertilizer reduction potential at the province scale and watershed scale, respectively. At the field scale, two consecutive years of field experiments were conducted on a tea plantation. Province-level analysis showed that 51.7% of the area had an average total fertilization intensity greater than 350 kg/hm2 and a high reduction potential. Watershed analysis revealed that chemical fertilizer reduction had better potential in reducing total nitrogen and total phosphorus inputs to runoff in the short term, whereas 50% organic fertilizer substitution was the best strategy to achieve long-term effects. The field experiments further proved that organic fertilizer substitution balanced tea growth and environmental protection. This study provides a useful method to investigate strategies to reduce chemical fertilizer use in tea-growing areas.


Assuntos
Fertilizantes , Nitrogênio , Agricultura , China , Fertilizantes/análise , Nitrogênio/análise , Fósforo/análise , Solo , Chá
10.
Gels ; 8(4)2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35448109

RESUMO

Spiropyran-containing hydrogels that can respond to external stimuli such as temperature, light, and stress have attracted extensive attention in recent years. However, most of them are generally dual or multiple stimuli-responsive to external stimuli, and the interplay of different stimulus responses is harmful to their sensitivity. Herein, spiropyran bearing polymer beads incorporated PAM (poly(AM-co-MA/DMSP3)) hydrogels with sole mechanochromic properties were synthesized by emulsion polymerization of acrylamide (AM) and methyl acrylate (MA) in the presence of spiropyran dimethacrylate mechanophore (DMSP3) crosslinker. Due to the hydrophobic nature of MA and DMSP3, the resultant hydrogel afforded a rosary structure with DMSP3 bearing polymer beads incorporated in the PAM network. It is found that the chemical component (e.g., AM, MA, and DMSP3 concentrations) significantly affect the mechanical and mechanoresponsive properties of the as-obtained poly(AM-co-MA/DMSP3) hydrogel. Under optimal conditions, poly(AM-co-MA/DMSP3) hydrogel displayed high mechanical properties (tensile stress of 1.91 MPa, a tensile strain of 815%, an elastic modulus of 0.67 MPa, and tearing energy of 3920 J/m2), and a good self-recovery feature. Owing to the mechanoresponsive of SP3, the hydrogels exhibited reversible color changes under force-induced deformation and relaxed recovery states. More impressive, the poly(AM-co-MA/DMSP3) hydrogel showed a linear correlation between tensile strain and chromaticity (x, y) as well as a stain and resting time-dependent color recovery rate. This kind of hydrogel is believed to have great potential in the application of outdoor strain sensors.

11.
Eur J Med Chem ; 231: 114155, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35121201

RESUMO

The natural product oridonin has the potential to be a broad-spectrum antineoplastic agent. To develop oridonin analogues with high potency, a series of novel oridonin analogues were designed and synthesized by removing the multiple hydroxyl groups of parent compound. The representative analogues 14, 19, and 26 exhibited potent anticancer effects against K562, MDA-MB-231, SMMC-7721, and MCF-7 cells. Further structural modification on their 14-OH generated more potent derivatives 16n, 21d, and 28d respectively, in which the IC50 value of compound 16n was 50-fold more potent than parent oridonin in K562 cells. Furthermore, compound 16n significantly induced the cell cycle arrest of K562 cells at the G2 phase and increased the fraction of apoptotic cells. Importantly, compounds 16n, 21d, and 28d exhibited good antitumor activities in H22 allograft mice in vivo. These results suggest that compounds 16n, 21d, and 28d deserve further development as promising candidates for the treatment of cancers.


Assuntos
Antineoplásicos , Diterpenos do Tipo Caurano , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Diterpenos do Tipo Caurano/química , Diterpenos do Tipo Caurano/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Relação Estrutura-Atividade
12.
Front Psychol ; 12: 661600, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093355

RESUMO

The purpose of this study was to explore the relationship between parenting styles and career decision-making difficulties in college students, and uncovered the mediating roles of core self-evaluation and career calling. A total of 1,127 undergraduates were recruited to complete the questionnaires about parenting styles, core self-evaluation, career calling, and career decision-making difficulties. The results showed that: (1) Positive and negative parenting styles could positively predict career decision-making difficulties in college students. (2) Core self-evaluation and career calling mediated the relationship between parenting styles and career decision-making difficulties. Sequential dual mediators only found in which positive paternal and maternal parenting styles predict career decision-making difficulties through core self-evaluation and career calling. (3) Further analysis revealed gender difference in the relationship between parenting styles and career decision-making difficulties. The relation between paternal positive parenting style and career decision-making difficulties was significant in male students, but absent in female students; the relation between maternal positive parenting and career decision-making difficulties and the relation between paternal negative parenting and career calling were significant in female students, but absent in male students; and the relation between career calling and career decision-making difficulties was greater in male than in female. The current study expanded and deepened those existing understandings about the relationship between parenting styles and adolescents' career decisions, so as to further reveal its internal mechanism and provide more reasonable suggestions and targeted guidance for career counseling.

13.
J Med Chem ; 64(13): 9120-9140, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34176264

RESUMO

A series of novel anaplastic lymphoma kinase (ALK) degraders were designed and synthesized based on proteolysis-targeting chimera (PROTAC) technology by linking two alectinib analogs (36 and 37) with pomalidomide through linkers of different lengths and types. The most promising degrader 17 possessed a high ALK-binding affinity and potent antiproliferative activity in the ALK-dependent cell lines and did not exhibit obvious cytotoxicity in ALK fusion-negative cells. More importantly, the efficacy of compound 17 in a Karpas 299 xenograft mouse model was further evaluated based on its ALK-sustained degradation ability in vivo. The reduction in tumor weight in the compound 17-treated group (10 mg/kg/day, I.V.) reached 75.82%, while alectinib reduced tumor weight by 63.82% at a dose of 20 mg/kg/day (P.O.). Taken together, our findings suggest that alectinib-based PROTACs associated with the degradation of ALK may have promising beneficial effects for treating ALK-driven malignancies.


Assuntos
Quinase do Linfoma Anaplásico/antagonistas & inibidores , Antineoplásicos/farmacologia , Carbazóis/farmacologia , Desenvolvimento de Medicamentos , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinase do Linfoma Anaplásico/metabolismo , Animais , Antineoplásicos/química , Carbazóis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Piperidinas/química , Inibidores de Proteínas Quinases/química , Proteólise/efeitos dos fármacos , Ratos , Relação Estrutura-Atividade
14.
J Biomed Nanotechnol ; 17(2): 312-321, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33785101

RESUMO

The establishment of sensing platform for trace analysis of Fe3+ in biological systems is meaningful for health monitoring. Herein, a Fe3+ sensitive fluorescent nanoprobe was constructed based on highly fluorescent N-doped carbon quantum dots (NCQDs) derived from bamboo stems through a hydrothermal method employing ethylenediamine as the nitrogen dopant. The prepared NCQDs had a uniformly distributed size and their mean size was around 2.43 nm. Abundant functional groups (C=N, N-H, C=O, and carboxyl) anchored on NCQDs demonstrated successful doping of N in CQDs. The obtained NCQDs possessed a high fluorescence quantum yield of 20.02% and outstanding fluorescence stability over a wide pH range and at high ionic strengths. Moreover, Fe3+ ions presented a specific fluorescent quenching effect to the as-prepared NCQDs. The calibration curve for fluorescence quenching degree corresponding to Fe3+ concentration showed a linear response in a range of 0.01-10 µM, and detection limit was 0.486 µM, which indicated that the NCQDs had high sensitivity to Fe3+ ions. Ascribed to these unique properties, the NCQDs were selected as luminescent probes for trace amount of Fe3+ ions in human serum. These results demonstrated their promising use in clinical diagnostics and other biologically relevant studies.


Assuntos
Pontos Quânticos , Carbono , Corantes Fluorescentes , Humanos , Íons , Nitrogênio , Espectrometria de Fluorescência
15.
Sci Total Environ ; 762: 143059, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33477247

RESUMO

Carbon (C) and nitrogen (N) inputs to farmland via fertilizer application are potential sources of C and N that influence soil acidification and water eutrophication. A pilot study was conducted to compare the effects of compound fertilizer and rapeseed cake organic fertilizer on C and N preservation in the soils and runoff of a tea plantation as well as the C and N isotopic fractionation in soils over the three annual cycles of fertilization and tea-leaf harvest. Overall, rapeseed cake organic fertilization effectively increased the pH, total organic matter, NH4-N and NO3-N in soils by 2.19-4.29%, 8.04-21.14%, 53.65-100.32% and 5.74-54.08%, respectively, but decreased NH4-N inputs in runoff by 10.36-25.12% and NO3-N inputs in runoff by 8.94-24.10% relative to the same rate of pure N in compound fertilizer. Before fertilization in February, the average δ13C and δ15N were -25.15‰ and 1.88‰, while after a full year of fertilization and tea-leaf harvesting in October, the average soil δ13C and δ15N contents were -23.83‰ and -0.33‰ after compound fertilization and -26.22‰ and 1.64‰ after rapeseed cake organic fertilization, respectively, indicating the evident effects of fertilization on the isotopic fractionation in soil. In addition, the fractionation extent was positively associated with the fertilization rates under both fertilizers. However, the two fertilization types had different effects on the C and N isotope fractionations, with rapeseed cake organic fertilization contributing more to δ13C (21.07-81.80%) but less to δ15N (18.20-78.93%) and compound fertilization presenting the opposite results (1.88-46.18% and 53.82-98.12%, respectively). This study demonstrates that rapeseed cake organic fertilization can better preserve soil C and N pools while reducing their runoff in tea plantations, which may greatly hinder the regional soil acidification and water eutrophication trends.

16.
J Med Chem ; 63(15): 8157-8178, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32610904

RESUMO

Triple-negative breast cancer (TNBC) is one of the most highly invasive and metastatic breast cancers without safe and effective therapeutic drugs. The natural product oridonin is reported to be a potential anti-TNBC agent. However, its moderate activity and complex structure hampered its clinical application. In this study, the novel oridonin analogues were first identified by removal of multiple hydroxyl groups and structural simplification of oridonin. The representative analogue 20 exhibited potent anticancer effects. Further structural modification on 20 generated the most potent derivative 56, which possessed 120-fold more potent antiproliferative activity than oridonin in the TNBC cell line HCC1806. Importantly, compound 56 exhibited more potent anticancer activity than paclitaxel in TNBC xenograft nude mice. Moreover, 56 could attenuate the expression of MMP-2, MMP-9, p-FAK, and integrin ß1 to inhibit TNBC cell metastasis. All results suggest that compound 56 may warrant further investigation as a promising candidate agent for the treatment of TNBC.


Assuntos
Diterpenos do Tipo Caurano/química , Diterpenos do Tipo Caurano/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
17.
J Mater Chem B ; 8(27): 5952-5961, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32667025

RESUMO

Rational design and fabrication of bio-nanoprobes for intracellular miRNA biosensing are highly desired for early clinical diagnosis and prognosis. Herein, we have developed a versatile LRET-based ratiometric (LBRU) nanoprobe of NaYF4:Yb,Er@NaYF4@NH2-mSiO2/rhodamine B/C-DNA sandwich-structured nanocomposites for intracellular miRNA biosensing. The nanoprobe was composed of NaYF4:Yb,Er@NaYF4 upconversion nanoparticles (energy donor) with an amino functionalized mesoporous silica shell (NH2-mSiO2), rhodamine B (acceptor) loaded into the mesopores of NH2-mSiO2, and the complementary sequences of target miRNA (denoted as C-DNA) acting as recognition species wrapped on the nanocomposite. Due to the LRET behavior between donors and acceptors, the loaded rhodamine B can quench the green upconversion emission of NaYF4:Yb,Er@NaYF4 at 540 nm completely. Moreover, it can be released from the nanocomposite in the presence of target miRNA, which blocked the LRET behavior to "turn on" the green upconversion luminescence. Besides, as the unaffected red upconversion luminescence (at 660 nm) can be used as an internal standard to provide built-in correction for environmental effects, the intensity ratio of upconversion luminescence at 540 and 660 nm (I540/I660) was employed as the output signal to afford an accurate detection of target miRNA. Due to the biocompatibility, high photostability and low auto-fluorescence background, the nanoprobe was successfully utilized to diagnose the intracellular miRNA-21 expression in MCF-7 cells via upconversion fluorescence imaging. We envision that the proposed LBRU nanoprobe has great potential applications in early cancer diagnosis.


Assuntos
Corantes Fluorescentes/química , Elementos da Série dos Lantanídeos/química , Nanopartículas Metálicas/química , MicroRNAs/análise , Técnicas Biossensoriais , Transferência Ressonante de Energia de Fluorescência , Expressão Gênica , Humanos , Células MCF-7 , Microscopia de Fluorescência , Nanocompostos/química , Imagem Óptica , Rodaminas/química , Dióxido de Silício/química
18.
Sci Total Environ ; 726: 138550, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32304946

RESUMO

The bioaccumulation and trophic transfer of As along food webs in freshwater ecosystems remain largely unknown. In this study, multiple environmental and biological samples were collected from a closed realgar mining area in South China. The As concentrations in the surface water, sediments and soils in the mining area were 0.62-3293 µg/L, 9.53-4543 mg/kg and 7.32-5008 mg/kg, respectively, and gradually decreased with distance from the central mining sites, indicating that historic As mining activities had an eminent impact on As contamination around the mine. The As concentrations in aquatic organisms ranged from 0.60 mg/kg to 45.75 mg/kg and varied markedly among sites and species, reflecting the influence of various physiologic and environmental factors. Arsenic species identified by liquid chromatography inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) were mainly organic, comprising 8% to 66% of the total As. Both the proportions and concentrations of inorganic As were positively correlated with total As. This correlation could be attributed to the higher assimilation and accumulation of inorganic As or the lower biotransformation ability of inorganic As with the increasing total As in the studied organisms. Values of δ13C and δ15N in aquatic organisms ranged from -30.59‰ to -15.07‰ and from 4.31‰ to 12.98‰, respectively, indicating multiple trophic levels and variety in the diet sources of these organisms. The δ15N increased distinctly in the order of planktivorous

Assuntos
Arsênio/análise , Poluentes Químicos da Água/análise , Animais , Organismos Aquáticos , Arsenicais , Bioacumulação , China , Ecossistema , Monitoramento Ambiental , Peixes , Cadeia Alimentar , Isótopos , Sulfetos
19.
J Nanosci Nanotechnol ; 20(3): 1511-1519, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492314

RESUMO

Recently, lanthanide-doped upconversion luminescent materials have showed great potential in optical data storage, information encryption and anti-counterfeiting. However, the low upconversion luminescence still limited their applications. In this work, we fabricated RGB NaYF4:Ln3+@NaYF4 core-shell nanoparticles (CSNPs) with enhanced upconversion luminescence by coating an inert NaYF4 shell onto NaYF4:Ln3+ core nanoparticles via thermal decomposition method. The effect of increased shell temperature and addition of shell precursors on crystal phase, morphology and luminescent property of the synthesized CSNPs were systematically investigated. It was demonstrated that high shell growing temperature facilitated the formation of pure ß-NaYF4 CSNPs. Upon increasing amount of shell precursors, the morphologies of hexagonal phase NaYF4 CSNPs changed from nanorod to nanocube and showed different luminescent properties. Pure hexagonal phase NaYF4 CSNPs with highest upconversion luminescence of about 15 times higher than NaYF4:Ln3+ core nanoparticles can be prepared at 310 °C with the addition of shell precursors at 3 mmol. Moreover, three-primary-color (RGB) CSNPs with enhanced upconversion luminescence were successfully prepared by changing the doping pair of lanthanide ions in core. The synthesized RGB CSNPs were fabricated into environment friendly luminescent ink by sequential surface modification by PAA ligand and dispersing in mixture solvent of ethanol, water and glycerol. Comparative results showed that the fluorescence enhanced RGB CSNPs inks were more suitable for inkjet printing of multicolored, complex and high resolution luminescent anti-counterfeiting patterns on paper substrates.

20.
J Nanosci Nanotechnol ; 20(3): 1866-1872, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492354

RESUMO

Upconversion nanocrystals with uniform size and hydrophilic surface have potential applications in biological medical engineering. In this study, hydrophilic NaYF4:Yb, Er nanospheres were synthesized via hexadecylpyridinium chloride (CPC) mediated hydrothermal process. The synthesized NaYF4:Yb, Er upconversion nanospheres (UCNSs) were characterized by various characterization methods. Results showed that the synthesized UCNSs exhibited a uniform sphere-like structure with average diameter of ~250 nm. The surface of UCNSs was captured by CPC molecule indicating hydrophilic properties of UCNSs. The spherical UCNSs composed of mixed phase (α+ß) NaYF4 nanocrystals. This is the novel study for synthesis of NaYF4:Ln3+ crystal employing CPC as ligand. Moreover, the effect of CPC concentration on synthesis of UCNSs was investigated by comparatively studying morphology, crystal phase and luminescent properties of desired sample prepared under different experimental conditions. It was found that high concentrations of CPC ligands were more favorable for forming NaYF4 crystal nanospheres with morphology that is more regular, have smoother surface, with higher crystallinity and better upconversion fluorescent properties. The possible growing mechanism was proposed and growing of NaYF4:Yb, Er nanospheres followed the classical Ostwald ripening process.

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