RESUMO
Fluorescence imaging in the near-infrared II (NIR-II, 1000-1700 nm) region opens up new avenues for biological systems due to suppressed scattering and low autofluorescence at longer-wavelength photons. Nonetheless, the development of organic NIR-II fluorophores is still limited mainly due to the shortage of efficient molecular design strategy. Herein, we propose an approach of designing Janus NIR-II fluorophores by introducing electronic donors with distinct properties into one molecule. As a proof-of-concept, fluorescent dye 2 TT-m, oC6B with both twisted and planar electronic donors displayed balanced absorption and emission which were absent in its parent compound. The key design strategy for Janus molecule is that it combines the merits of intense absorption from planar architecture and high fluorescence quantum yield from twisted motif. The resulting 2 TT-m, oC6B nanoparticles exhibit a high molar absorptivity of 1.12 ⨯104 M-1 cm-1 at 808 nm and a NIR-II quantum yield of 3.7%, displaying a typical aggregation-induced emission (AIE) attribute. The highly bright and stable 2 TT-m, oC6B nanoparticles assured NIR-II image-guided cancer surgery to resect submillimeter tumor nodules. The present study may inspire further development of molecular design philosophy for highly bright NIR-II fluorophores for biomedical applications.
RESUMO
We determined the alleles of ten single nucleotide poly-morphisms (SNPs) in the APOA5/A4/C3/A1 gene cluster and in APOB in Han Chinese from Xinjiang Shihezi, China using MALDI-TOF mass spectrometry, and explored the correlation between these SNPs and dyslipidemia through a case-control study design with 250 pa-tients and 250 normal controls. All SNPs except for APOA5 rs2072560 conformed to Hardy-Weinberg equilibrium (all P > 0.05). APOA5 rs651821, APOA4 rs5104, APOC3 rs734104, and APOC3 rs5128 geno-type and allele frequencies were significantly different between groups (all P < 0.01). For rs651821, the risks of dyslipidemia for the CC or CC+CT genotypes were 9.917 or 1.859 times that of TT, and the risk of the C vs T allele was 2.027. For rs5104, the AG, GG, or AG+GG risks were 1.797, 1.861, and 1.809 times AA, and the G vs A risk was 1.427. For rs734104, the CT, CC, or CC+CT risks were 1.851, 2.570, and 1.958 times TT, and the C vs T risk was 1.610. For rs5128, the GC or CC+GC risks were 1.738 or 1.749 times GG, and the C vs G risk was 1.477. Compared with the wild-type haplotype TATG, the risks of dyslipidemia with CGCC, TGCC, or CATG haplotypes (odds ratios = 2.434, 1.503, and 2.740, respectively) were significantly higher. Our results suggested that these four SNPs were significantly associated with dyslipidemia in Xinjiang Shihezi Han Chinese, and might serve as risk factors for dyslipidemia. Individuals carrying the CGCC, TGCC, or CATG haplotypes were prone to dyslipidemia.
Assuntos
Apolipoproteína C-III/genética , Apolipoproteínas A/genética , Apolipoproteínas B/genética , Dislipidemias/genética , Estudos de Associação Genética , Família Multigênica , Polimorfismo de Nucleotídeo Único , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
We examined the effect of microRNAs on 3T3-L1 adipocyte differentiation and expression of adipocyte-specific gene fatty acid-binding protein 4 (FABP4). We screened and identified adipo-related microRNAs during 3T3-L1 adipocyte differentiation with a microRNA microarray. High expression plasmids of miR-24 and miR-21 were constructed and transfected into 3T3-L1 preadipocytes by lipofectamine. The effects of miR-24 and miR-21 on 3T3-L1 adipocyte differentiation were observed, and the protein and mRNA expression levels of FABP4 and AP-1 were determined. The expression profiles of microRNAs significantly changed during 3T3-L1 adipocyte differentiation. The expression of 33 microRNAs was downregulated, among which downregulation of miR-24 was the most extensive. There were 17 microRNAs with upregulated expression; the highest levels were found for miR-21. miR-24 significantly inhibited 3T3-L1 adipocyte differentiation and maturity, while miR-21 had no significant effect. In addition, miR-24 significantly inhibited the expression of FABP4, while it upregulated AP-1 expression, but had no effect on the level of FABP4 mRNA. miR-21 had no effect on FABP4 protein and mRNA expression. AP-1 silencing could, at least partially, reverse the inhibitory effect of miR-24 on FABP4 expression. We conclude that microRNA expression profiles change significantly during 3T3- L1 adipocyte differentiation and that miR-24 plays an important role in regulating adipocyte differentiation and FABP4 expression. The mechanism involved may be the upregulation of AP-1.
Assuntos
Adipócitos/citologia , Adipócitos/metabolismo , Diferenciação Celular/genética , Proteínas de Ligação a Ácido Graxo/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Células 3T3-L1 , Animais , Proteínas de Ligação a Ácido Graxo/metabolismo , Perfilação da Expressão Gênica , Camundongos , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismoRESUMO
The P-element has been successfully used in germline transformation to create transgenic flies and as an insertion mutagenesis agent to disrupt genes. Moreover, P-element can also be used to knockout genes that are near the insertion sites by inducing its imprecise transposition. In this article, P-element insertion lines were crossed with transposase expression fly to recover the transposon, and the deletion of flanking sequence, which was created by imprecise excision, was detected by PCR. Through this method, null alleles of seven genes that spread over three major chromosomes (X, second, third) were generated in Drosophila melanogaster. Results show that the frequency of flanking deletions is expected to be 1%, and it is enough to pick up at least one ideal deletion line from 200 independent recovery lines in general. These data suggest that although the frequency of disrupted gene varied greatly, from 0.13 to 2.34%, gene knockout by inducing P-element transposition appears to be a feasible and effective strategy, compared to the complicated process of gene targeting based on homologous recombination.