Negatively Curved Octagon-Incorporated Aza-nanographene and its Assembly with Fullerenes.

A negatively curved aza-nanographene (NG) containing two octagons was synthesized by a regioselective and stepwise cyclodehydrogenation procedure, in which a double aza[7]helicene was simultaneously formed as an intermediate. Their saddle-shaped structures with negative curvature were unambiguously confirmed by X-ray crystallography, thereby enabling the exploration of the structure-property relationship by photophysical, electrochemical and conformational studies. Moreover, the assembly of the octagon-embedded aza-NG with fullerenes was probed by fluorescence spectral titration, with record-high binding constants (Ka=9.5×103 M-1 with C60, Ka=3.7×104 M-1 with C70) found among reported negatively curved polycyclic aromatic compounds. The tight association of aza-NG with C60 was further elucidated by X-ray diffraction analysis of their co-crystal, which showed the formation of a 1 : 1 complex with substantial concave-convex interactions.

Self-Immolative Photosensitizers for Self-Reported Cancer Phototheranostics.

Photosensitizers to precise target and change fluorescence upon light illumination could accurately self-report where and when the photosensitizers work, enabling us to visualize the therapeutic process and precisely regulate treatment outcomes, which is the unremitting pursuit of precision and personalized medicine. Here, we report self-immolative photosensitizers by adopting a strategy of light-manipulated oxidative cleavage of C═C bonds that can generate a burst of reactive oxygen species, to cleave to release self-reported red-emitting products and trigger nonapoptotic cell oncosis. Strong electron-withdrawing groups are found to effectively suppress the C═C bond cleavage and phototoxicity via studying the structure-activity relationship, allowing us to elaborate NG1-NG5 that could temporarily inactivate the photosensitizer and quench the fluorescence by different glutathione (GSH)-responsive groups. Thereinto, NG2 with 2-cyano-4-nitrobenzene-1-sulfonyl group displays excellent GSH responsiveness than the other four. Surprisingly, NG2 shows better reactivity with GSH in weakly acidic condition, which inspires the application in weakly acidic tumor microenvironment where GSH elevates. To this end, we further synthesize NG-cRGD by anchoring integrin αvß3 binding cyclic pentapeptide (cRGD) for tumor targeting. In A549 xenografted tumor mice, NG-cRGD successfully deprotects to restore near-infrared fluorescence because of elevated GSH in tumor site, which is subsequently cleaved upon light irradiation releasing red-emitting products to report photosensitizer working, while effectively ablating tumors via triggered oncosis. The advanced self-immolative organic photosensitizer may accelerate the development of self-reported phototheranostics in future precision oncology.

Synthesis of a π-Extended Double [9]Helicene.

Double helicenes are appealing chiral frameworks. Their π-extension is desirable to achieve (chir)optical response in the visible and near-infrared (NIR) region, but access to higher double [n]helicenes (n≥8) has remained challenging. Herein, we report an unprecedented π-extended double [9]helicene (D9H), unambiguously revealing its structure by single-crystal X-ray diffraction. D9H shows remarkable NIR emission from 750 to 1100 nm with a high photoluminescence quantum yield of 18 %. In addition, optically pure D9H exhibits panchromatic circular dichroism with a notable dissymmetry factor (gCD ) of 0.019 at 590 nm, which is among the highest in the visible region for reported helicenes.

The putative mature peptide of piscidin-1 modulates global transcriptional profile and proliferation of splenic lymphocytes in orange-spotted grouper (Epinephelus coioides).

Piscidins are important components in protecting microbial infections in teleost. The present study purified and identified a truncated peptide, whose sequence was very close to that of putative mature peptide of epinecidin-1 (piscidin-1) in orange-spotted grouper (Epinephelus coioides), Epi-1 (also named as short form of ecPis-1, ecPis-1S). The immunomodulatory effects of ecPis-1S on splenic lymphocytes of orange-spotted grouper were explored in vitro. The transcriptome study was carried out by De novo transcriptome sequencing (RNA-Seq) in splenic lymphocytes of orange-spotted grouper. Regarding the profiles of gene expressions, 2994 genes were up-regulated and 2679 genes were down-regulated in the splenic lymphocytes stimulated by ecPis-1S. In the case of differential expression genes, 330 genes were involved in immune related pathways. Among them, 34 genes were involved in T cell receptor signaling pathway, 31 genes in natural killer cell mediated cytotoxicity and 23 genes in leukocyte transendothelial migration, respectively. Immune-related genes selected for qRT-PCR verification, such as interleukin-1ß (il-1b), tumor necrosis factor α (tnfa), T cell antigen receptor (tcr), major histocompatibility complex class I (mhc I), and mhc II were significantly up-regulated by ecPis-1S (p < 0.05). ecPis-1S could significantly enhance the proliferation of splenic lymphocytes of orange-spotted grouper in vitro (p < 0.05). In addition, the result of qRT-PCR revealed that ecPis-1S also significantly up-regulated cell cycle-related genes, including cyclin A (cyca), cyclin-dependent kinase 2 (cdk2), cdk4, cell division cycle protein 6 (cdc6), and transforming growth factor ß (tgfb) (p < 0.05), which suggested that ecPis-1S promoted the proliferation of lymphocytes by activating cell division cycle. In conclusion, the results indicated that the mature peptide of piscidin-1 in orange-spotted grouper could act as immune modulator and play an important role in regulation of the immune response in fish.

Ratiometric Polymer Probe for Detection of Peroxynitrite and the Application for Live-Cell Imaging.

Peroxynitrite (ONOO-) is one of the sources of oxidation stress involved in many biological signaling pathways. The role of ONOO- being a double-edged sword in biological systems drives the development of effective detection tools. In this work, a boronate-based polymeric fluorescent probe PB-PVA was synthesized and the probe performance was evaluated. The probe exhibits ratiometric sensing of ONOO- in a range of 0-6 µM. There is good linear relationship between the probe fluorescence intensity ratio and ONOO- concentration. The probe also displays moderate selectivity towards ONOO- over other ROS. Moreover, it is water-soluble and possesses good biocompatibility which aids the imaging of ONOO- in living cells. These properties could make the probe a promising tool in in vitro study related to ONOO-.

Crystal structure of 5-[bis-(4-eth-oxy-phenyl)amino]-thio-phene-2-carbaldehyde.

In the title compound, C21H21NO3S, the planes of the two benzene rings are nearly perpendicular to one another [dihedral angle = 84.50 (10)°] and they are oriented with respect to the plane of the thio-phene ring at dihedral angles of 59.15 (9) and 66.61 (9)°. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming supra-molecular chains propagating along the b-axis direction.

Low-temperature plasma-activated medium enhances the chemosensitivity of colorectal cancer cells by improving hypoxia.

Studies have demonstrated that the tumour microenvironment is hypoxia and that hypoxia can induce hypoxia inducible factor-1α (HIF-1α) expression and mediate tumour chemoresistance, which leads to a very poor prognosis for cancer patients. In this study, an economical and practical HIF-1α inhibitor, plasma-activated medium (PAM), was prepared, and its role in colorectal cancer (CRC) was investigated in vitro and in vivo. We found that HIF-1α expression significantly increased under hypoxia in CRC cells followed by decreased chemosensitivity to oxaliplatin (OXA). Additionally, PAM could reduce HIF-1α expression induced by hypoxia in CRC cells, and compared to PAM or OXA alone, PAM enhanced the chemosensitivity of OXA both in vitro in CRC cells and in vivo in cell-derived xenografts, as indicated by the inhibition of cell proliferation and tumour growth. Further mechanistic studies revealed that PAM might exert synergistic antitumour activity by inhibiting the MAPK pathway, which deserves further elucidation. In summary, PAM displayed prospective clinical application due to its important function in improving hypoxia in CRC.

Rational Design of Oxazolidine-Based Red Fluorescent pH Probe for Simultaneous Imaging Two Subcellular Organelles.

A reversible pH-responsive fluorescent probe, BP, was rationally designed and synthesized, based on protonation and deprotonation gave rise to oxazolidine ring open and close. The fluorescence response of BP against pH ranges from 3.78 to 7.54, which is suitable for labeling intracellular pH-dependent organelles. BP displayed strong red emission at a relatively high pH in living HeLa cells and U87 cells. More importantly, this probe exhibited good colocalization with both mitochondria and lysosomes in these two cell lines, attributing to pH-induced structure tautomerism resulting in an oxazolidine ring open and close that triggered effective targeting of these two organelles. As organelle interactions are critical for cellular processes, this strategy of targeting dual organelles through the structure tautomerism is conducive to further developing more effective and advanced probes for real-time imaging of the interaction between mitochondria and lysosomes.

Double Thia/sulfone[7]helicenes with Controlled Photophysical and Chiroptical Properties by Heteroatom Variation.

The development of helicenes with strong chiroptical response and controlled photophysics is highly desirable but challenging. In this work, double thia/sulfone[7]helicenes were synthesized to investigate the heteroatom effect on the photophysical and chiroptical properties of double heterohelicenes through comparison with the previously reported double oxa[7]helicene. By variation of the embedded heteroatoms from oxygen to sulfur, the absorption and emission were significantly red-shifted, along with the improved luminescence dissymmetry factor (glum ). In particular, the double sulfone[7]helicene exhibited strong red to near-infrared (NIR) emission with glum of 1.1×10-3 , suggesting its potential as a NIR circularly polarized luminescence emitter.

Electron-Deficient Contorted Polycyclic Aromatic Hydrocarbon via One-Pot Annulative π-Extension of Perylene Diimide.

The synthesis of a class of contorted electron-deficient polycyclic aromatic hydrocarbons (PAHs) has been achieved by a one-pot bay annulation of perylene diimide involving a mild Suzuki coupling and subsequent air-mediated, ambient-light-induced photocyclization. X-ray crystallography unambiguously confirmed the contorted PAH structure bearing four imide groups. The photophysical and electronic properties of these contorted PAHs were also analyzed, showing a high fluorescence quantum yield of 86% and moderate electron mobility of 0.017 cm2 V-1 s-1.

S-Shaped Double Helicene Diimides: Synthesis, Self-Assembly, and Mechanofluorochromism.

Herein we present a synthesis of an S-shaped double helicene with fused imide moieties, achieving a contorted aromatic diimide (DHDI) with good fluorescence properties in both solution and the solid state. DHDI demonstrates distinct mechanofluorochromism from yellow to green emission under grinding of its crystalline powder.

RNA N6-methyladenosine reader IGF2BP3 regulates cell cycle and angiogenesis in colon cancer.

BACKGROUND: N6-Methyladenosine (m6A) modification has been implicated in multiple processes for colon cancer development. IGF2BP3 was a newly reported m6A reader, whereas its role in colon cancer remains unclear. METHODS: The expression of m6A associated enzymes and total m6A level were measured by Western Blotting analysis and m6A RNA Methylation Quantification Kit respectively. Cell cycle was analyzed by flowcytometry. The interaction of IGF2BP3 and related targets was analyzed by RNA immunoprecipitation (RIP) and m6A RNA immunoprecipitation (MeRIP) assays. RESULTS: We investigated all m6A regulated enzymes in colon cancer and found only the overexpression of IGF2BP3 was associated with cancer progression and survival based on The Cancer Genome Atlas (TCGA) databases. Additionally, we also demonstrated IGF2BP3 was associated with DNA replication in the cell cycle. Knockdown of IGF2BP3 significantly repressed percentage of S phase of cell cycle as well as cell proliferation. Further research demonstrated IGF2BP3 bound to the mRNA of Cyclin D1 (CCND1, checkpoint of G1/S phase of cell cycle) and reduced its mRNA stability via reading m6A modification in the CDS region. Overexpression of Cyclin D1 in IGF2BP3 down-regulated cells completely rescued the inhibited percentage of S phase in cell cycle as well as cell proliferation. Additionally, we also demonstrated a similar role of IGF2BP3 at VEGF. IGF2BP3 bound to the mRNA of VEGF and reads m6A modification, thus regulated both expression and stability of VEGF mRNA. Knockdown of IGF2BP3 repressed angiogenesis in colon cancer via regulating VEGF. CONCLUSION: Knockdown of IGF2BP3 repressed DNA replication in the S phase of cell cycle and angiogenesis via reading m6A modification of CCND1 and VEGF respectively. IGF2BP3 was a possible prognosis marker and potential therapeutic target of colon cancer.

Nanoreactors for Chemical Synthesis and Biomedical Applications.

With the rapid development of nanoscience and nanotechnology, various types of functional nanoreactors have been designed for diverse applications. Here, the recent evolution of the rational design of nanoreactors for chemical synthesis and biomedical applications are briefly summarized and discussed. The presence of nanoreactors provides constrained space isolated from the surrounding environment. Scientists are committed to studying changes in chemical reactions when the reaction system is confined to the nanosized space. Nanoreactors accelerate the reaction rate and even change mechanism of some chemical reactions. Cells and organelles as natural nanoreactors are also discussed. The development of intracellular synthesis makes it possible to realize various applications in biomedicine. The challenges on the rational design of nanoreactors and perspectives are also discussed.

Reaction-based chiroptical sensing of ClO- using circularly polarized luminescence via self-assembly organogel.

By covalent combination of a chiral amino acid, lipid, and achiral phenothiazine derivative, a reaction-based chiroptical probe, PTZ-D, was obtained. PTZ-D could self-assemble into a chiral organogel realizing the chirality transformation from a chiral amino acid to a self-assembled system and displaying unprecedented chiroptical monitoring of ClO- with switchable CPL signals.

Spiro[pyrrol-benzopyran]-based probe with high asymmetry for chiroptical sensing via circular dichroism.

This contribution describes an efficient approach to constructing chiral spiro[pyrrol-benzopyran] (SPP) scaffold with high asymmetry. By combining chiral SPP and the achiral sensing moiety phenothiazine, the target probe P showed unprecedented reaction-based chiroptical sensing towards hypochlorite with switching CD signals.

Reductive cleavage of C[double bond, length as m-dash]C bonds as a new strategy for turn-on dual fluorescence in effective sensing of H2S.

Reductive cleavage of alkenes is rarely reported in synthetic chemistry. Here we report a unique H2S-mediated reductive cleavage of C[double bond, length as m-dash]C bonds under mild conditions, which is a successful new strategy for the design of probes for effective sensing of H2S with turn-on dual-color fluorescence. A short series of phenothiazine ethylidene malononitrile derivatives were shown to react with H2S, via reductive cleavage of C[double bond, length as m-dash]C bonds with intramolecular cyclization reactions to form thiophene rings. Enlightened by this new reaction mechanism, four effective probes with turn-off to turn-on fluorescence switches were successfully applied for sensing H2S, an important gaseous signalling molecule in living systems, among which PTZ-P4 exhibited two fluorescent colors after reductive cleavage. The dual-color probe was applied for imaging endogenous H2S and showed distinct differences in brightness in living C. elegans for wild type N2, glp-1 (e2144) mutants (higher levels of endogenous H2S), and cth-1 (ok3319) mutants (lower levels of endogenous H2S). The discovery of H2S-mediated reductive cleavage of C[double bond, length as m-dash]C bonds is expected to be valuable for chemical synthesis, theoretical studies, and the design of new fluorescent H2S probes.

Thiophene-based terpyridine and its zinc halide complexes: third-order nonlinear optical properties in the near-infrared region.

A novel 4'-(4-(diphenylamino)thienyl)-2,2':6',2''-terpyridine ligand () based on thiophene and its complexes (X = Cl, Br, I, SCN) was designed, synthesized and characterized by elemental analysis, far-IR, MALDI-TOF-MS, and single crystal X-ray diffraction analysis. Structural studies revealed that the central zinc(ii) atom adopted a distorted trigonal bipyramidal coordination model. However, there were different hydrogen bonds and stacking models with different counter anions in the crystals. The absorption properties of the compounds were investigated with the aid of TD-DFT computational methods. Furthermore, the third-order nonlinear optical (NLO) properties were systematically studied via open-aperture Z-scan methods using a tunable wavelength femtosecond laser. The results from photophysical property investigations suggested that the complexation of the thiophene-based terpyridine ligand with zinc halides resulted in strong ICT/LLCT bands of about 450 nm, and the complexes exhibited strong nonlinear optical response in the near-infrared range around 850 nm. Above all, the two-photon absorption (2PA) cross-section values (σ) were enhanced by coordination with zinc and influenced by halide ions, reaching up to 2583 GM (X = Br).