Synthesis and Characterization of SiO2/nGO/Fe3O4/SeQDs Nanoparticles as Potential Nanocarriers in Drug Delivery Systems.

Herein, we constructed the branch-shaped SiO2/nano GO (nGO)/Fe3O4/selenium quantum dots (QDs) (SeQDs) nanoparticles (SGF/SeQDs) embodying magnetism, fluorescence, and microwave stimulus response properties to enhance the performance of releasing drugs. The SGF/SeQDs composite was characterized by technologies including powder X-ray diffraction, transmission electron microscopy, infrared spectroscopy, etc. In the nanoparticles, the branch-shaped SiO2 provides a large specific surface area, nGO as the dielectric loss-style material promotes microwave-absorbing performance, and the Fe3O4 serves as a magnetic targeting agent and microwave absorber. Integrating nGO and Fe3O4 could further strengthen the microwave absorption of the entire composite; selenium features both fluorescence and anticancer effects. The synthesized nanoparticles as carriers exhibited a branch-like mesoporous sphere of ∼260 nm, a specific surface area of 258.57 m2 g-1, a saturation magnetization of 24.59 emu g-1, and good microwave thermal conversion performance that the temperature was elevated from 25 to 70 °C under microwave irradiation. These physical characteristics, including large pore volume (5.30 nm), high specific surface area, and fibrous morphology, are in favor of loading drugs. Meanwhile, the cumulative etoposide (VP16) loading rate of the nanoparticles reached to 21 wt % after 360 min. The noncovalent interaction between the VP16 and SGF/SeQDs was mainly the hydrogen-bonding effect during the loading process. Furthermore, the drug release rates at 180 min were up to 81.46, 61.92, and 56.84 wt % at pH 4, 5, and 7, respectively. At 25, 37, and 50 °C, the rates of drug release reach 25.40, 56.84, and 65.32 wt %, respectively. After microwave stimulation at pH 7, the rate of releasing drug increased distinctly from 56.84 to 71.74 wt % compared to that of nonmicrowave irradiation. Cytotoxicity tests manifested that the carrier had good biocompatibility. Therefore, the nanoparticles are looking forward to paving one platform for further applications in biomedicine and drug delivery systems.

Up-regulation of CREB-1 regulates tendon adhesion in the injury tendon healing through the CREB-1/TGF-ß3 signaling pathway.

AIM: To explore the mechanism of the healing of tendon tissue and anti-adhesion, and to discuss the role of the transforming growth factor-ß3 (TGF-ß3)/cAMP response element binding protein-1 (CREB-1) signaling pathway in the healing process of tendons. METHOD: All mice were divided into four groups of 1, 2, 4, and 8 weeks respectively. Each time group was divided into four treatment groups: the amplification group, the inhibition group, the negative group, and the control group. When the tendon injury model was established, the CREB-1 virus was injected into the tendon injury parts. A series of methods such as gait behaviourism, anatomy, histological examination, immunohistochemical examination and collagen staining were employed to assess the tendon healing and the protein expression of TGF-ß3, CREB-1, Smad3/7 and type I/III collagen (COL-I/III). CREB-1 virus was sent to tendon stem cells to assess the protein expression of TGF-ß1, TGF-ß3, CREB-1, COL-I/III by methods such as immunohistochemistry and Western blot. RESULTS: The amplification group showed better gait behaviourism than the inhibition group in the healing process. The amplification group also had less adhesion than the negative group. Hematoxylin-eosin (HE) staining of tendon tissue sections showed that the number of fibroblasts in the amplification group was less than the inhibition group, and the immunohistochemical results indicated that the expression of TGF-ß3, CREB-1, and Smad7 at each time point was higher than the inhibition group. The expression of COL-I/III and Smad3 in the amplification group was lower than the inhibition group at all time points. The collagen staining indicated that the ratio of type I/III collagen in the amplification group was higher than the negative group at 2,4,8 week. The CREB-1 amplification virus could promote the protein expression of TGF-ß3, CREB-1 and inhibit the protein expression of TGF-ß1 and COL-I/III in the tendon stem cells. CONCLUSION: In the process of tendon injury healing, CREB-1 could promote the secretion of TGF-ß3, so as to promote the tendon healing and have the effect of anti-adhesion in tendons. It might provide new intervention targets for anti-adhesion treatment of tendon injuries.

Reversible [4 + 2] Photooxygenation in Anion-Coordination-Driven-Assembled A2L2-Type Complexes.

Two bis-bis(urea) ligands (L1 and L2) incorporating the photoactive 9,10-diphenylanthracene fragment were designed for the construction of anion-coordination-driven assemblies and subsequent oxygenation of anthracene moieties for singlet oxygen storage. The corresponding A2L2-type sulfate complexes [TEA]4[(SO4)2(L1)2] (1) and [TEA]4[(SO4)2(L2)2] (2), where TEA = tetraethylammonium, were achieved by coordinating the ligands L1 or L2 with sulfate anions. Both 1 and 2 were able to undergo [4 + 2] photooxygenation to form endoperoxide photoproducts 1-EPO and 2-EPO, which can be partially converted back to the original anthracene compounds after heating. The structures of 1-EPO and 2-EPO were unambiguously confirmed by X-ray crystallography, NMR and UV-vis spectroscopy, and high-resolution electrospray ionization mass spectrometry.

4'-SCF3 -Labeling Constitutes a Sensitive 19 F NMR Probe for Characterization of Interactions in the Minor Groove of DNA.

Fluorinated nucleotides are invaluable for 19 F NMR studies of nucleic acid structure and function. Here, we synthesized 4'-SCF3 -thymidine (T 4 ' - SCF 3 ${{^{4{^\prime}\hbox{-}{\rm SCF}{_{3}}}}}$ ) and incorporated it into DNA by means of solid-phase DNA synthesis. NMR studies showed that the 4'-SCF3 group exhibited a flexible orientation in the minor groove of DNA duplexes and was well accommodated by various higher order DNA structures. The three magnetically equivalent fluorine atoms in 4'-SCF3 -DNA constitute an isolated spin system, offering high 19 F NMR sensitivity and excellent resolution of the positioning of T 4 ' - SCF 3 ${{^{4{^\prime}\hbox{-}{\rm SCF}{_{3}}}}}$ within various secondary and tertiary DNA structures. The high structural adaptability and high sensitivity of T 4 ' - SCF 3 ${{^{4{^\prime}\hbox{-}{\rm SCF}{_{3}}}}}$ make it a valuable 19 F NMR probe for quantitatively distinguishing diverse DNA structures with single-nucleotide resolution and for monitoring the dynamics of interactions in the minor groove of double-stranded DNA.

C4'-Fluorinated Oligodeoxynucleotides: Synthesis, Stability, Structural Studies.

Fluoro-substitution on the ribose moiety (e. g., 2'-F-deoxyribonucleotide) represents a popular way to modulate the ribose conformation and, hence, the structure and function of nucleic acids. In the present study, we synthesized 4'-F-deoxythymidine (4'-F T) and introduced it to oligodeoxyribonucleotides (ODNs). Though scission of the glycosylic bond of 4'-F T followed by strand cleavage occurred to some extent under alkaline conditions, the 4'-F T-modified ODNs were rather stable in neutral buffers. NMR studies showed that like 2'-F-deoxyribonucleoside, 4'-F T exists predominantly in the North conformation not only in the nucleoside form but also in the context of ODN strands. Circular dichroism spectroscopy, thermal denaturing and RNase H1 footprinting studies of 4'-F T-modified ODN/cDNA and ODN/cRNA duplexes indicated that the North conformation tendency of 4'-F T is maintained in the duplexes, leading to a local structural perturbation. Collectively, 4'-F-deoxyribonucleotide structurally resembles the 2'-F-deoxyribonucleotide but imparts less structural perturbation to the duplex than the latter.

Gait analysis combined with the expression of TGF-ß1, TGF-ß3 and CREB during Achilles tendon healing in rat.

PURPOSE: To observe the changes of gait behavior and the expression of wound healing factors of transforming growth factor-ß1 (TGF-ß1), TGF-ß3 and cAMP response element binding protein-1 (CREB-1) during the healing of Achilles tendon in a rat model, and to investigate whether gait analysis can be used to evaluate the tendon healing. METHODS: Achilles tendon of 40 healthy male Sprague-Dawley rats were transected and sutured to establish the Achilles tendon injury (ATI) model. They were randomly divided into 4 groups based on the observational time point at 1, 2, 4 and 6 weeks after injury (n = 10 for each group). Before modeling, 9 rats were randomly selected for CatWalk gait analysis, which contained step cycle, single stance time and average speed. Data were recorded as the normal controls. After then, ATI models were established in the left hind limbs of the all 40 rats (ATI group), while the right hind limbs were only cut and sutured without injury of the Achilles tendon (sham operation group). At 1, 2, 4 and 6 weeks after injury, the gait behavior of the corresponding group of rats (n = 9) as observed and recorded by CatWalk platform. After then, the rats were sacrificed and Achilles tendon of both limbs was harvested. The tendon healing was observed by gross anatomy and histological examination, and the protein and mRNA expression of TGF-ß1, TGF-ß3, CREB-1 were observed by immunohistochemistry and qPCR. The results of tendon gross grading were analyzed by Wilcoxon rank sum test, and other data were analyzed by one-way analysis of variance among multiple groups. RESULTS: Compared with normal controls, all gait indexes (step cycle, single stance time and average speed) were greatly affected following ATI, which however improved with time. The step cycle was significantly lower at 1, 2 and 4 weeks after ATI (compared with normal controls, all p < 0.05), but almost returned to the normal level at 6 weeks ((0.694 ± 0.102) vs. (0.503 ± 0.094) s, p > 0.05). The single stance time of the ATI group was significantly shorter at 1 and 2 weeks after operation ((0.078 ± 0.010) s at 1 week, (0.078 ± 0.020) s at 2 weeks, all p < 0.001) and revealed no significant difference at 4 weeks (p = 0.120). The average speed of ATI group at 1, 2, 4, 6 weeks was significantly lower than that in the normal control group (all p < 0.001). Gross observation showed that the grade of local scar adhesion in ATI group increased significantly at 2, 4 and 6 weeks, compared with the sham operation group (all p < 0.001). Extensive adhesion was formed at 6 weeks after ATI. The results of HE staining showed that the number of fibroblast increased gradually and arranged more orderly in ATI group at 1, 2 and 4 weeks (all p < 0.001), and decreased at 6 weeks, but it was still significantly higher than that of the sham operation group (p < 0.001). Immunohistochemistry showed that the positive expression of TGF-ß1, TGF-ß3, CREB-1 in ATI group was higher than that in the sham operation group at 4 time points (all p < 0.05), which reached the peak at 2 weeks after operation and decreased at 4 weeks (p = 0.002, p < 0.001, p = 0.041, respectively). The results of qPCR suggested that the mRNA expression of TGF-ß1, TGF-ß3, CREB-1 in ATI group was higher than that in the sham operation group at all-time points (all p < 0.05), which reached the peak at 2 weeks after operation, decreased at 4 weeks, and significantly decreased at 6 weeks (all p < 0.001). CONCLUSION: Gait behavior indexes are associated with Achilles tendon healing. The study gives an insight of TGF-ß1, TGF-ß3, CREB-1 changes in the coursing of Achilles tendon healing and these cytokines may be able to be used to regulate the Achilles tendon healing.

4'-Fluorinated RNA: Synthesis, Structure, and Applications as a Sensitive 19F NMR Probe of RNA Structure and Function.

Fluorinated RNA molecules, particularly 2'-F RNA, have found a wide range of applications in RNA therapeutics, RNA aptamers, and ribozymes and as 19F NMR probes for elucidating RNA structure. Owing to the instability of 4'-F ribonucleosides, synthesis of 4'-F-modified RNA has long been a challenge. In this study, we developed a strategy for synthesizing a 4'-F-uridine (4'FU) phosphoramidite, and we used it to prepare 4'-F RNA successfully. In the context of an RNA strand, 4'FU, which existed in a North conformation, was reasonably stable and resembled unmodified uridine well. The 19F NMR signal of 4'FU was sensitive to RNA secondary structure, with a chemical shift dispersion as large as 4 ppm (compared with <1 ppm for 2'FU), which makes it a valuable probe for discriminating single-stranded RNA and A-type, B-type, and mismatched duplexes. In addition, we demonstrated that because RNA-processing enzymes treated 4'FU the same as unmodified uridine, 4'FU could be used to monitor RNA structural dynamics and enzyme-mediated RNA processing. Taken together, our results indicate that 4'-F RNA represents a probe with wide utility for elucidation of RNA structure and function by means of 19F NMR spectroscopy.

Linkage engineering in hosts for dramatic efficiency enhancement of blue phosphorescent organic light-emitting diodes.

Higher triplet energy and balanced charge mobility is two key factors for high-efficiency host materials of phosphorescent organic light-emitting diodes (PhOLED), which are integrated in a carbazole-diphenylene-fluorene hybrid FDPCz2 (9,9'-(4',4"-(9H-fluorene-9,9-diyl)bis(biphenyl-4',4-diyl))bis(9H-carbazole)) on the basis of indirect linkage strategy. Owing to rationally spatial allocation of conjugation blocking and extension for diphenylene linkages, FDPCz2 achieves both high triplet energy of 2.97 eV and favorable charge mobility by order of 6.3 × 10(-6) cm(2) V(-1) s(-1). Compared to conventional hosts and a short-conjugated analogue FPCz2 (9,9'-(4,4'-(9H-fluorene-9,9-diyl)bis(4,1-phenylene)) bis(9H-carbazole)), FDPCz2 dramatically elevated device efficiencies with peak values of 40.6 cd A(-1) and 20.2% for blue PhOLEDs.

Photo-caged 2-butene-1,4-dial as an efficient, target-specific photo-crosslinker for covalent trapping of DNA-binding proteins.

Covalent trapping of DNA-binding proteins via photo-crosslinking is an advantageous method for studying DNA-protein interactions. However, traditional photo-crosslinkers generate highly reactive intermediates that rapidly and non-selectively react with nearby functional groups, resulting in low target-capture yields and high non-target background capture. Herein, we report that photo-caged 2-butene-1,4-dial (PBDA) is an efficient photo-crosslinker for trapping DNA-binding proteins. Photo-irradiation (360 nm) of PBDA-modified DNA generates 2-butene-1,4-dial (BDA), a small, long-lived intermediate that reacts selectively with Lys residues of DNA-binding proteins, leading in minutes to stable DNA-protein crosslinks in up to 70% yield. In addition, BDA exhibits high specificity for target proteins, leading to low non-target background capture. The high photo-crosslinking yield and target specificity make PBDA a powerful tool for studying DNA-protein interactions.

Dibenzothiophene Sulfone-Based Phosphine Oxide Electron Transporters with Unique Asymmetry for High-Efficiency Blue Thermally Activated Delayed Fluorescence Diodes.

Three asymmetrical electron transporters as dibenzothiophene sulfone (DBSO)-diphenylphosphine oxide (DPPO) hybrids, collectively named mnDBSODPO, were designed and prepared. All of these materials achieve the high triplet energy of ∼3.0 eV to restrain the exciton linkage from emissive layers. The dependence of inductive and steric effects for DPPO groups on the substitution position, the intermolecular interaction suppression, the encapsulations of high-polar DBSO cores, and the favorable electrical performance are successfully integrated on 36DBSODPO, which can simultaneously suppress the exciton quenching by formation of an interfacial dipole and enhancing the charge flux balance. As a result, 36DBSODPO endowed its tetralayer blue thermally activated delayed fluorescence (TADF) devices with impressive performance, including the maximum external quantum efficiency around 19%, and reduced efficiency roll-offs, which verifies the great potential of asymmetrical electron transporting materials for highly efficient TADF devices.

Optimizing the Intralayer and Interlayer Compatibility for High-Efficiency Blue Thermally Activated Delayed Fluorescence Diodes.

A series of phosphine oxide hosts, 4,6-bis(diphenylphosphoryl) dibenzothiophene (DBTDPO) and 4- diphenylphosphoryldibenzothiophene (DBTSPO), and electron transporting materials (ETM), 2-(diphenylphosphoryl)dibenzothiophene sulfone (2DBSOSPO), 3-(diphenylphosphoryl)dibenzothiophene sulfone (3DBSOSPO) and 4-(diphenylphosphoryl)dibenzothiophene sulfone (4DBSOSPO) were developed to support blue thermally activated delayed fluorescence (TADF) devices with high performance through optimizing intralayer and interlayer compatibility of emissive layers. On the basis of the triplet energy of ~3.0 eV for the hosts and ETMs, excitons can be effectively confined on DMAC-DPS. Compared to DBTSPO, DBTDPO can support the excellent distribution uniformity to blue TADF dye bis[4-(9,9-dimethyl-9,10-dihydroacridine) phenyl] sulfone (DMAC-DPS), owing to their configuration similarity; while 3DBSOSPO and 4DBSOSPO are superior in compatibility with the hosts due to the similar molecular polarity or configuration. Through adjusting the molecular configuration, the electrical performance of ETMs can be feasibly tuned, including the excellent electron mobility (µe) by the order of 10(-3) cm(2) V(-1) s(-1). As the result, DBTDPO and 4DBSOSPO endowed their four-layer blue TADF devices with the maximum current efficiency of 33.5 cd A(-1) and the maximum external quantum efficiency more than 17%, which are impressive among the best blue TADF devices. It is showed that intralayer compatibility determines the maximum efficiencies, while interlayer compatibility influences efficiency stability.