Mitochondrial UQCC3 controls embryonic and tumor angiogenesis by regulating VEGF expression.

Mitochondria play important roles in angiogenesis. However, the mechanisms remain elusive. In this study, we found that mitochondrial ubiquinol-cytochrome c reductase complex assembly factor 3 (UQCC3) is a key regulator of angiogenesis. TALEN-mediated knockout of Uqcc3 in mice caused embryonic lethality at 9.5-10.5 days postcoitum, and vessel density was dramatically reduced. Similarly, knockout of uqcc3 in zebrafish induced lethality post-fertilization and impaired vascular development. Knockout of UQCC3 resulted in slower tumor growth and angiogenesis. Mechanistically, UQCC3 was upregulated under hypoxia, promoted reactive oxygen species (ROS) generation, enhanced HIF-1α stability and increased VEGF expression. Finally, higher expression of UQCC3 was associated with poor prognosis in multiple types tumors, implying a role for UQCC3 in tumor progression. In conclusion, our findings highlight the important contribution of UQCC3 to angiogenesis under both physiological and pathological conditions, indicating the potential of UQCC3 as a therapeutic target for cancer.

Cyclo-Ketal Xanthene Dyes: A New Class of Near-Infrared Fluorophores for Super-Resolution Imaging of Live Cells.

Newly emerging super-resolution imaging techniques provide opportunities for precise observations on cellular microstructures. However, they also impose severe demands on fluorophores. Here, we develop a new series of NIR xanthene dyes, named as KRhs, by replacing the 10-position O of rhodamines with a cyclo-ketal. KRhs display an intense NIR emission peak at 700 nm with fluorescence quantum yields up to 0.64. More importantly, they, without the aid of enhancing buffer, exhibit stochastic fluorescence off-on switches to support time-resolved localization of single fluorophore. KRhs are functionalized into KRh-MitoFix, KRh-Mem and KRh-Halo that demonstrate mitochondria, plasma membrane and fusion protein targeting ability, respectively. Consequently, these KRh probes demonstrate straightforward usage for super-resolution imaging of these targets in live cells. Therefore, KRhs merit future development for fluorescence labeling and super-resolution imaging in the NIR region.

Catalyst-Free One-Pot Synthesis of Unsymmetrical Five- and Six-Membered Sulfur-Annulated Heterocyclic Perylene Diimides for Electron-Transporting Property.

A novel unsymmetrical five- and six-membered sulfur-annulated heterocyclic perylene diimides (PDI) derivative was obtained by a one-pot and catalyst-free synthesis in a high yield. The unsymmetrical PDI exhibits a noteworthy bathochromic shift absorption of up to 700 nm and a low-lying lowest unoccupied molecular orbital level of -3.99 eV. The compound owns a complete planar structure and a high electron mobility of 4.8 × 10-3 cm2 V-1 s-1 in solution-processable top-gate/bottom-contact organic field-effect transistor device.

Specifically and wash-free labeling of SNAP-tag fused proteins with a hybrid sensor to monitor local micro-viscosity.

Viscosity, as one of the major factors of intracellular microenvironment, influences the function of proteins. To detect local micro-viscosity of a protein, it is a precondition to apply a viscosity sensor for specifically target to proteins. However, all the reported small-molecule probes are just suitable for sensing/imaging of macro-viscosity in biological fluids of entire cells or organelles. To this end, we developed a hybrid sensor BDP-V BG by connecting a viscosity-sensitive boron-dipyrromethene (BODIPY) molecular rotor (BDP-V) to O6-benzylguanine (BG) for specific detection of local micro-viscosity of SNAP-tag fused proteins. We measured and calculated the reaction efficiency between the sensor and SNAP-tag protein in vitro to confirm the high labeling specificity. We also found that the labeling reaction results in a 53-fold fluorescence enhancement for the rotor, which qualifies it as a wash-free sensor with ignorable background fluorescence. The high sensitivity of protein labeled sensor (BDP-V-SNAP) to the changes of local viscosity was evaluated by detecting the enhancement of fluorescence lifetimes. Further, with the sensor BDP-V BG, we achieved high specific labeling of cells expressing two SNAP-tag fused proteins (nuclear histone H2B and mitochondrial COX8A). Two-photon excited fluorescence lifetime imaging revealed that, the micro-viscosities nearby the SNAP-tag fused two proteins are distinct. The different changes of local micro-viscosity of SNAP-tag fused histone protein in apoptosis induced by three nucleus-targeted drugs were also characterized for the first time.

Monitoring lipid peroxidation within foam cells by lysosome-targetable and ratiometric probe.

Lipid peroxidation (LPO) in lysosomes is a valuable analyte because it is close associated with the evolutions of some major diseases. As a typical example, in the start-up phase of atherosclerosis, lysosomes get as swollen as foams, by accumulating a large amount of lipoproteins, which facilitates the free-radical chain propagation of LPO. Despite the existences of several fluorescent LPO probes, they are not appropriate for reporting the local extents of lysosomal LPO, for their unspecific intracellular localizations. Here, Foam-LPO, the first fluorescent LPO probe specifically targeting lysosomes, has been developed through straightforward synthesis using low-cost reagents. A basic tertiary amine group enables it to selectively localize in acidic lysosomes; and the conjugated diene moiety within the BODIPY fluorophore will degrade in response to lipid peroxidation, which results in fluorescence maximum shifting from 586 to 512 nm. Thus, under a confocal fluorescence microscope, Foam-LPO is able not only to visualize dynamic morphological changes of lysosomes during the evolution of foam cells, but also to relatively quantify local LPO extents in single lysosomes through ratiometric imaging. In addition, Foam-LPO proves applicable for two-color flow cytometry (FCM) analysis to make quantitative and high-throughput evaluation of LPO levels in large quantity of cells at different stages during the induction to form foam cells. Also importantly, with the aid of this new probe, the different roles played by low-density lipoprotein (LDL) and its oxidized form (ox-LDL) for the LPO processes of foam cells are distinguished and clarified, which benefits the understanding in the initiation and control factors of atherosclerosis.

Bipolar and fixable probe targeting mitochondria to trace local depolarization via two-photon fluorescence lifetime imaging.

Polarization/depolarization levels of different single mitochondria in a cell are inhomogeneous, and always varying. Because depolarization is an indicator of mitochondrial dysfunction, tracing local depolarization is highly desirable. The existing fluorescent probes, however, are not well suited for this task, although they are applicable to assess the average polarization extents of whole cells. A multifunctional and bipolar probe MITFPS is thus developed, which includes a positively charged hydrophilic group and an environment sensitive fluorophore. In the probe design, the hydrophilic anchoring unit is chemically immobilized on a membrane protein, while the lipophilic fluorophore can be inserted deep into the phospholipid layer. The probe exhibits a sensitive response to the local variation in polarization by changing its fluorescence lifetime. MITFPS's applicability is confirmed by real-time in situ imaging of the complete process of an uncoupler-induced depolarization under a two-photon fluorescence lifetime microscope. The imaging result reveals that one mitochondrion could have quite different polarization than the other, even though they are in the same cell.

Controllable and stepwise synthesis of soluble ladder-conjugated bis(perylene imide) fluorenebisimidazole as a multifunctional optoelectronic material.

By a controllable and stepwise strategy, a soluble ladder-conjugated perylene derivative BPI-FBI as the only product has been synthesized, which avoids the tough work to isolate regioisomers generated by a conventional one-step condensation method. BPI-FBI exhibits broad absorption spectra covering the whole visible region from 300 to 700 nm because of the large π-conjugation skeleton and has a low LUMO level inheriting the prototype PDI. In the steady-state space-charge-limited current (SCLC) devices, BPI-FBI exhibits an intrinsic electron mobility of 1.01 × 10(-5) cm(2) V(-1) s(-1). With a high two photon absorbing activity in the near-infrared region from 1200 to 1400 nm, BPI-FBI also exhibits good optical limiting performance, which will be useful for sensor or human eye protection and stabilization of light sources for optical communications.

A soluble ladder-conjugated star-shaped oligomer composed of four perylene diimide branches and a fluorene core: synthesis and properties.

A new ladder-conjugated star-shaped oligomer electron-transporting material TetraPDI-PF, with four perylene diimide (PDI) branches and a fluorene core, was efficiently synthesized. The oligomer is highly soluble in dichlorobenzene with a solubility of 155 mg mL(-1), which is higher than those of PDI (35 mg mL(-1)) and PDI-Phen (70 mg mL(-1)). Demonstrated by thermogravimetric analysis (TGA), the oligomer exhibits excellent thermal stability with the decomposition temperature (Td) of 291.2 °C, which is 65 °C higher than that of PDI. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were employed to investigate the electrochemical properties. Although the CV curves of TetraPDI-PF are successively scanned for 15 cycles, they still remain invariable reduction potentials. The oligomer also shows outstanding photostability, even better than PDI, which maintains 99 % fluorescence intensity after irradiation for 10 min using maximum laser intensity. In the steady-state space-charge-limited current (SCLC) devices, TetraPDI-PF exhibits higher intrinsic electron mobility of 2.22×10(-5) cm(2) V(-1) s(-1), three orders of magnitude over that of PDI (3.52×10(-8) cm(2) V(-1) s(-1)). The bulk heterojunction (BHJ) organic solar cells (OSCs) using TetraPDI-PF as non-fullerene acceptors and P3HT as donors give optimum power conversion efficiency (PCE) of 0.64 %, which is 64 times that of the PDI:P3HT BHJ cells.

Chemically modified graphene oxides as a hole transport layer in organic solar cells.

We demonstrate O(2) plasma treated graphene oxides with a work function of 5.2 eV as a high performance hole transport layer in organic solar cells. The high transparency and high work function simultaneously increase short circuit current, threshold voltage and fill factor, resulting in a 30% increase in cell efficiency.

Self-host heteroleptic green iridium dendrimers: achieving efficient non-doped device performance based on a simple molecular structure.

Self-host heteroleptic green iridium(III) dendrimers have been designed and easily synthesized. Through tuning the carbazole dendron density, high efficiency is achieved using these dendrimers with a simple molecular structure as the emitting layer for the non-doped organic light-emitting diodes.

Bipolar heteroleptic green iridium dendrimers containing oligocarbazole and oxadiazole dendrons for bright and efficient nondoped electrophosphorescent devices.

Bipolar heteroleptic green light-emitting iridium (Ir) dendrimers G(OXD) and G(DOXD) have been designed and synthesized under mild conditions in high yields, in which the first C^N and second O^O ligands are functionalized with oligocarbazole- and oxadiazole-based dendrons, respectively. To avoid affecting the optical properties of the emissive iridium core, all the functional moieties are attached to the ligands through a flexible spacer. Compared with the unipolar dendrimer G(acac), dendrimers G(OXD) and G(DOXD) exhibit the close emission maxima of 511-512 nm and photoluminescence quantum yield of 0.39-0.40 in a solution of toluene. Moreover, on going from G(acac) to G(OXD) and G(DOXD), we have found that the introduction of oxadiazole fragments decreases the lowest unoccupied molecular orbital (LUMO) energy levels to facilitate the electron injection and electron transporting, while their highest occupied molecular orbital (HOMO) energy levels remain unchanged. This means that, we can individually tune the HOMO and LUMO energy levels based on the heteroleptic structure to ensure the relative independence between the hole and electron in the emitting layer (EML), which is a favorable feature for bipolar optoelectronic materials. As a result, a bilayer nondoped electrophosphorescent device with G(DOXD) as the EML gives a maximum luminous efficiency of 25.5 cd A(-1) (η(ext): 7.4%) and a brightness of 33,880 cd m(-2). In comparison to G(acac) (17.2 cd A(-1), 17,680 cd m(-2)), both the efficiency and brightness are improved by about 1.5 and 2 times, respectively. These state-of-the-art performances indicate the potential of these bipolar heteroleptic iridium dendrimers as solution-processible emitting materials for nondoped device applications.