72 research outputs found

    Glucose Oxidase–Polymer Nanogels for Synergistic Cancer-Starving and Oxidation Therapy

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    Glucose oxidase (GOX) can convert glucose into gluconic acid and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), which is potentially useful for synergistic cancer-starving and oxidation therapy. Herein we demonstrate a glucose-responsive nanomedicine made of GOX–polymer nanogels to regulate H<sub>2</sub>O<sub>2</sub> production for synergistic melanoma starving and oxidation therapy. GOX–polymer nanogels showed glucose-responsive H<sub>2</sub>O<sub>2</sub>-generating activity in vitro, improved stability, and considerably enhanced tumor retention as compared to native GOX. More importantly, they exhibited high antimelanoma efficacy and no obvious systemic toxicity, whereas native GOX was ineffective and systemically toxic at the same dose. This work paves the way for establishing an endogenous and noninvasive cancer treatment paradigm that is based on intratumoral glucose-responsive, H<sub>2</sub>O<sub>2</sub>-generating chemical reactions

    Least squares mean (LSM) ± standard error for the fear level of different <i>STMN1</i> SNPs in English Springer Spaniel.

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    <p>Least squares mean (LSM) ± standard error for the fear level of different <i>STMN1</i> SNPs in English Springer Spaniel.</p

    Genetic Variants in the STMN1 Transcriptional Regulatory Region Affect Promoter Activity and Fear Behavior in English Springer Spaniels

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    <div><p>Stathmin 1 (<i>STMN1</i>) is a neuronal growth-associated protein that is involved in microtubule dynamics and plays an important role in synaptic outgrowth and plasticity. Given that STMN1 affects fear behavior, we hypothesized that genetic variations in the <i>STMN1</i> transcriptional regulatory region affect gene transcription activity and control fear behavior. In this study, two single nucleotide polymorphisms (SNPs), g. -327 A>G and g. -125 C>T, were identified in 317 English Springer Spaniels. A bioinformatics analysis revealed that both were loci located in the canine <i>STMN1</i> putative promoter region and affected transcription factor binding. A statistical analysis revealed that the TT genotype at g.-125 C>T produced a significantly greater fear level than that of the CC genotype (<i>P</i> < 0.05). Furthermore, the H4H4 (GTGT) haplotype combination was significantly associated with canine fear behavior (<i>P</i> < 0.01). Using serially truncated constructs of the <i>STMN1</i> promoters and the luciferase reporter, we found that a 395 bp (−312 nt to +83 nt) fragment constituted the core promoter region. The luciferase assay also revealed that the H4 (GT) haplotype promoter had higher activity than that of other haplotypes. Overall, our results suggest that the two SNPs in the canine <i>STMN1</i> promoter region could affect canine fear behavior by altering <i>STMN1</i> transcriptional activity.</p></div

    Public attention, big data technology, and green innovation efficiency: empirical analysis based on spatial metrology

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    This study employs the undesirable output super-efficiency SBM-DEA model to reassess the green innovation efficiency (GIE) of 30 Chinese provinces from 2011 to 2020. We pioneer the examination of public attention (PA) influence on GIE and spatial spillover effects, employing the spatial Durbin model. Additionally, a spatial mediation model, incorporating big data technology as a mediator, is adopted. Key findings are as follows: 1) Significant spatial correlations exist in PA and GIE. 2) Improved PA in one province can help enhance the GIE in neighboring provinces but cannot directly impact the local GIE. 3) The positive impact of PA on local GIE follows an indirect path. Specifically, PA elevates the level of big data technology in the local and neighboring provinces, and this positive technological spillover effect significantly enhances the GIE across the entire region. 4) Industrial structure and research and development intensity also influence GIE to some extent.</p

    Self-assembly and morphology transition of amphipathic spiropyran-based random copolymers to control drug release

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    <p>An amphipathic spiropyran-based random copolymer P(SPMA-co-DMAEMA) was synthesized by atom transfer radical polymerization, and the resulting copolymer was characterized by means of <sup>1</sup>H nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, and gel permeation chromatography. The self-assembly behaviors and morphology transition were systematically investigated under single and combined external environmental stimuli by transmission electron microscopy. With coumarin 102 as the model drug molecule, the self-assembly micelles were used to control drug loading, release, and re-encapsulation to some extent. The characterization results indicated the successful preparation of the spiropyran-based random copolymer P(SPMA-co-DMAEMA). The external stimuli had some influences on the morphology of the self-assembly aggregate, and the ‘schizophrenic’ behavior was interestingly found in this work. The drug release experiments showed the reversible loading and release process up to a point, which might expand the potential application domain of the amphiphilic spiropyran-based random copolymer in drug delivery.</p

    <i>STMN1</i> promoter transcriptional activity and the recombinant haplotypes.

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    <p>(A) 5′-flanking region of canine <i>STMN1</i>, as identified using the NCBI database. Grey box represents exon 1. g. -327 A>G and g. -125 C>T are located in the <i>STMN1</i> 5′-flanking region (−2,304 nt to +83 nt). Other numbers represent primer positions for the cloning reporter constructs. (B) The P-F5 fragment with different haplotypes (H1, H2, H3, and H4) was amplified by polymerase chain reaction to generate the reporter constructs; the various recombinant haplotypes are shown above the line. Each fragment was cloned into the pGL3 basic vector and transfected into 293T cells. (C) <i>STMN1</i> promoter transcriptional activities with various haplotypes were measured by dual luciferase assays. Results are normalized firefly luciferase activity to Renilla luciferase activity for each sample. The pGL3-basic reporter vector was used as a control. Compared with the basal activity of control, the promoter activity of all haplotype constructs was higher (*<i>P <</i> 0.05). Compared with the H4 activity, H1 and H2 showed significant lower activity (#<i>P <</i> 0.05).</p

    Primers used in this study.

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    <p>Primers used in this study.</p

    Genotype distribution, allelic frequencies, and genetic diversity of the two single nucleotide polymorphisms (SNPs) in canine stathmin 1 (<i>STMN1</i>).

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    <p>Genotype distribution, allelic frequencies, and genetic diversity of the two single nucleotide polymorphisms (SNPs) in canine stathmin 1 (<i>STMN1</i>).</p

    Genetic variation in the canine <i>STMN1</i> 5′-flanking region sequence and polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) patterns.

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    <p>(A) Sequencing diagrams using DNA pools of g. -327 A>G. (B) Sequencing diagrams using DNA pools of g. -125 C>T. (C) Electrophoresis patterns of PCR-SSCP at position g. -327 A>G, 1 = GG, 2 = AG, and 3 = AA. (D) Electrophoresis patterns of PCR-SSCP at position g. -125 C>T, 4 = CC, 5 = CT, and 6 = TT.</p

    Multiple sequence alignments of the <i>STMN1</i> core promoter region among six species.

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    <p>(A) The black box presents <i>PMF1</i> binding site. (B) The two black boxes present <i>Nkx6</i>.<i>3</i> and <i>FOXP1</i> binding site respectively. Nucleotides are numbered relative to the dog <i>STMN1</i> gene transcription start site. Sequence consistent with dog <i>STMN1</i> is labeled by asterisk, and a gap is represented by a hyphen (-). Nucleotides shown in bold and underlined font represent differences from the dog regulatory elements.</p
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