Hyperbranched Tetraphenylethylene Derivatives with Low Non-specific Aggregation-Induced Emission for Fluorescence Recognition of Proteins with Hydrophobic Pockets

Proteins play an important role in the physiological process of many organisms, and their abnormal level often indicates the occurrence of some diseases. Therefore, protein analysis has important reference value and clinical significance for early diagnosis and therapy of disease. Using human serum albumin (HSA) as a model protein, a series of super-branched tetraphenylethylene (TPE) derivatives with different branching structures and terminal groups are reported herein for highly sensitive and specific recognition of proteins with hydrophobic cages. Benefiting from the hyperbranched structures, these probes showed much higher critical micelle concentrations (CMCs) than most linear TPE-based amphiphilic molecules since the hyperbranched structure not only improved their solubility but also amplified the steric hindrance effect and electrostatic repulsive force to prevent their aggregation. Dynamic light scattering experiments proved that these probes formed dense aggregates at CMC, and such aggregate structures would lead to a higher background fluorescence noise. Hence, a higher CMC is more conducive to the detection of the target with low backgrounds. Among them, P3-COOH with −COOH as the terminal unit and a relatively longer branch showed the highest CMC and the best signal to background ratio (S/N). Mechanism studies showed that P3-COOH was bound to HSA mainly through a hydrophobic force, resulting in a limited P3-COOH molecular movement and less attack from quenchers in solutions, thus leading to greatly enhanced fluorescence intensity. In addition, P3-COOH was also applied to the determination of HSA content in actual human serum samples

Ratiometric Fluorescence Imaging of Intracellular MicroRNA with NIR-Assisted Signal Amplification by a Ru-SiO₂@Polydopamine Nanoplatform

Accurate and sensitive fluorescence imaging of intracellular miRNA is essential for understanding the mechanism underlying some physiological and pathological events, as well as the prevention and diagnosis of diseases. Herein, a highly sensitive ratiometric fluorescent nanoprobe for intracellular miRNA imaging was fabricated by integrating a Ru-SiO2@polydopamine (Ru-SiO2@PDA) nanoplatform with a near-infrared light (NIR)-assisted DNA strand displacement signal amplification strategy. The Ru-SiO2@PDA spheres have excellent biosafety, high photothermal effect, and unique photophysical properties that can both emit a stable red fluorescence and well quench the fluorophores getting closer to them. So, when the fuel DNA and carboxyfluorescein (FAM)-labeled signal DNA are co-assembled on their outer surfaces, the FAM’s green fluorescence is quenched, and a low ratiometric signal is obtained. However, in the presence of miRNA, the target displaces the signal DNA from the capture DNA, releasing the signal DNA far away from the Ru-SiO2@PDA. Then, the green fluorescence recovers and leads to an enhanced Igreen/Ired value. Under NIR light irradiation, the Ru-SiO2@PDA increases the local temperature around the probe and triggers the release of fuel DNA, which thus recycles the target miRNA and effectively amplifies the ratiometric signal. Using A549 cells as a model, the nanoprobe realizes the highly sensitive ratiometric fluorescence imaging of miRNA let-7a, as well as its in vivo up- and down-regulation expressions. It provides a facile tool for highly sensitive and accurate intracellular miRNA detection through one-step incubation and may pave a new avenue for single-cell analysis

Ratiometric Fluorescence Imaging of Intracellular MicroRNA with NIR-Assisted Signal Amplification by a Ru-SiO₂@Polydopamine Nanoplatform

Accurate and sensitive fluorescence imaging of intracellular miRNA is essential for understanding the mechanism underlying some physiological and pathological events, as well as the prevention and diagnosis of diseases. Herein, a highly sensitive ratiometric fluorescent nanoprobe for intracellular miRNA imaging was fabricated by integrating a Ru-SiO2@polydopamine (Ru-SiO2@PDA) nanoplatform with a near-infrared light (NIR)-assisted DNA strand displacement signal amplification strategy. The Ru-SiO2@PDA spheres have excellent biosafety, high photothermal effect, and unique photophysical properties that can both emit a stable red fluorescence and well quench the fluorophores getting closer to them. So, when the fuel DNA and carboxyfluorescein (FAM)-labeled signal DNA are co-assembled on their outer surfaces, the FAM’s green fluorescence is quenched, and a low ratiometric signal is obtained. However, in the presence of miRNA, the target displaces the signal DNA from the capture DNA, releasing the signal DNA far away from the Ru-SiO2@PDA. Then, the green fluorescence recovers and leads to an enhanced Igreen/Ired value. Under NIR light irradiation, the Ru-SiO2@PDA increases the local temperature around the probe and triggers the release of fuel DNA, which thus recycles the target miRNA and effectively amplifies the ratiometric signal. Using A549 cells as a model, the nanoprobe realizes the highly sensitive ratiometric fluorescence imaging of miRNA let-7a, as well as its in vivo up- and down-regulation expressions. It provides a facile tool for highly sensitive and accurate intracellular miRNA detection through one-step incubation and may pave a new avenue for single-cell analysis

Ratiometric Fluorescence Imaging of Intracellular MicroRNA with NIR-Assisted Signal Amplification by a Ru-SiO₂@Polydopamine Nanoplatform

Accurate and sensitive fluorescence imaging of intracellular miRNA is essential for understanding the mechanism underlying some physiological and pathological events, as well as the prevention and diagnosis of diseases. Herein, a highly sensitive ratiometric fluorescent nanoprobe for intracellular miRNA imaging was fabricated by integrating a Ru-SiO2@polydopamine (Ru-SiO2@PDA) nanoplatform with a near-infrared light (NIR)-assisted DNA strand displacement signal amplification strategy. The Ru-SiO2@PDA spheres have excellent biosafety, high photothermal effect, and unique photophysical properties that can both emit a stable red fluorescence and well quench the fluorophores getting closer to them. So, when the fuel DNA and carboxyfluorescein (FAM)-labeled signal DNA are co-assembled on their outer surfaces, the FAM’s green fluorescence is quenched, and a low ratiometric signal is obtained. However, in the presence of miRNA, the target displaces the signal DNA from the capture DNA, releasing the signal DNA far away from the Ru-SiO2@PDA. Then, the green fluorescence recovers and leads to an enhanced Igreen/Ired value. Under NIR light irradiation, the Ru-SiO2@PDA increases the local temperature around the probe and triggers the release of fuel DNA, which thus recycles the target miRNA and effectively amplifies the ratiometric signal. Using A549 cells as a model, the nanoprobe realizes the highly sensitive ratiometric fluorescence imaging of miRNA let-7a, as well as its in vivo up- and down-regulation expressions. It provides a facile tool for highly sensitive and accurate intracellular miRNA detection through one-step incubation and may pave a new avenue for single-cell analysis

Knockdown of ADORA2A antisense RNA 1 inhibits cell proliferation and enhances imatinib sensitivity in chronic myeloid leukemia

Long non-coding RNAs (LncRNAs) exert important regulatory roles in chronic myeloid leukemia (CML). In this study, we aimed to investigate the potential role and molecular mechanism of lncRNA ADORA2A antisense RNA 1 (ADORA2A-AS1) in CML. We found that the expression of ADORA2A-AS1 was upregulated in CML. Further, knockdown of ADORA2A-AS1 inhibited the proliferation, induced apoptosis, arrested cell cycle, and enhanced imatinib sensitivity in CML cells. Besides, ADORA2A-AS1 promoted the expression of transforming growth factor-beta receptor 1 (TGFBR1) and ATP binding cassette subfamily C member 2 (ABCC2) via sponging miR-665, thereby exerting a tumor-promoting activity. Collectively, our results confirmed the oncogenic effect of ADORA2A-AS1 in CML, indicating that ADORA2A-AS1 is a promosing therapeutic target for CML.</p

Development of Triphenylamine Functional Dye for Selective Photoelectrochemical Sensing of Cysteine

A novel triphenylamine-based organic dye, TTA, with an acrylic group is designed to graft TiO₂ nanoparticles for sensitive and selective photoelectrochemical sensing. The synthesized TTA possesses a high molar absorption coefficient, leading to an enhanced photoelectron emission ability of the electron donor. The carboxyl group of TTA acts as not only an electron acceptor but also a linker to connect TTA to TiO₂ nanoparticles. Under irradiation, TTA shows fast intramolecular charge transfer from triphenylamine to carboxyl group via the π-bridge of thiophene moiety, thus producing a sensitive photocurrent response. Meanwhile, the acrylic moiety provides an active site for the Michael addition reaction, which would destroy the π-bridge and decrease the photocurrent response. Thus, a selective photoelectrochemical sensing strategy is proposed for detection of small biomolecules. Using cysteine as a model analyte, this sensing strategy shows a detectable range from 1 to 200 μM, without the interference from natural amino acids and various biological reducing reagents. This work offers a new photoelectrochemical route to highly selective and sensitive detection of biologically important small molecules

Supplementary Figures 1 - 8 from Transient Activation of Hedgehog Pathway Rescued Irradiation-Induced Hyposalivation by Preserving Salivary Stem/Progenitor Cells and Parasympathetic Innervation

PDF file - 2605K, Fig. S1. X-gal staining of SMG sections from Ptch1-lacZ mice non-treated (NT), 7 days after ligation of main excretory ducts or IR. Fig. S2. 7 days of Dox treatment did not rescue IR-induced hyposalivation in female KrtrtTA/ tetO-Shh mice and male wild type mice. (A) Relative saliva flow rate. (B) Relative expression of acinar markers Aqp5 and Chrm3 determined by qRT-PCR. Fig. S3. Transient Hh activation has no long-term effect on percentage of putative salivary stem/progenitor cells. Fig. S4. Effects of transient Hh activation on proliferation and IR-induced apoptosis of SMG cells. Fig. S5. Co-expression of makers for salivary stem/progenitor cells with Hh target genes. Fig. S6. Activation of Hh pathway in female mouse SMGs by SAG. Fig. S7. Morphology of cultured human salivary epithelial cells. Fig. S8. Effects of retrograde Shh gene transfer into SMGs on expression of Hh target genes and SCC VII tumor growth.</p

Additional file 4 of Effects of macrophages on the proliferation and cardiac differentiation of human induced pluripotent stem cells

Additional file 3. Supplemental Figure

Additional file 3 of Effects of macrophages on the proliferation and cardiac differentiation of human induced pluripotent stem cells

Additional file 2. Supplemental Table