Unraveling Dual Aggregation-Induced Emission Behavior in Steric-Hindrance Photochromic System for Super Resolution Imaging.

Unprecedented dual aggregation-induced emission (AIE) behavior based on a steric-hindrance photochromic system is presented, with incorporation one or two bulky aryl groups, resulting in different flexibleness. The dual AIE behavior of open and closed isomers can be explained by restriction of intramolecular rotation (RIR), restriction of intramolecular vibration (RIV), and intermolecular stacking. The large bulky benzothiophene causes restricted rotation, enhancing the emission of open form in solution and weak π-π molecular packing, thereby efficiently enhancing the luminescence performance in the solid state. With incorporation of two large bulky benzothiophene groups, BBTE possesses the most outstanding AIE activity, undergoing highly efficient and reversible off-to-on fluorescence in film upon alternating UV and visible light irradiation along with excellent fatigue resistance. The off-to-on fluorescent photoswitch is successfully established in super resolution imaging.

All-Visible-Light-Activated Dithienylethenes Induced by Intramolecular Proton Transfer.

The fast light-responsive dithienylethenes (DTEs) are one of the most attractive photochromic families because of their excellent thermal irreversibility and fatigue resistance. However, the all-visible-light-activated DTE system still remains challenging because most of them require the harmful high-energy ultraviolet light to trigger their photocyclization reaction. Here, we have for the first time borrowed a specific intramolecular proton transfer (IPT) process and rationally designed a series of all-visible-light-driven DTEs. Incorporating the IPT-functional group to DTE unit gives rise to an extra absorption band with a distinct red shift, which enables the photocyclization of DTEs under stimuli of visible light at 450 nm, as well as ensuring the desirable photoswitching efficiency. The isomerization from OH form to NH form induced by IPT can decrease the energy gap for excitation and photocyclization, thereby affording the all-visible-light-triggered photochromic performance, which can not only work well in a polar solvent system but also show its effectiveness in polymeric gel systems. In this regard, we can provide a general and reliable platform to construct all-visible-light-driven DTEs with excellent reversible photoswitching and broad applicability, especially with avoiding the use of harmful ultraviolet light to induce their photocyclization.

Conformer-dependent self-assembled metallacycles with photo-reversible response.

Discrete, well-defined metallacycles and metallacages with stimuli-responsive behaviors have been largely predominated by the organic donor/metal acceptor paradigm with spontaneous formation of coordination bonds. However, light-driven self-assembly systems usually show relatively low utilization yield of photons and low fatigue resistance. Given that almost no example illustrates the different self-assembly behaviors of antiparallel and parallel conformers in the traditional photochromic diarylethene (DAE) system, here we have for the first time constructed a unique series of photoactive conformer-dependent metallacycles, focusing on the characterization and comparison of self-assembly behavior in different ligand conformers with different di-platinum(ii) acceptors. Their photoswitchable scaffold sizes and shapes are precisely controlled by photochromically separable parallel or anti-parallel conformers via coordination-driven self-assembly. The ap-conformer and closed form provide larger bending angles upon coordination with di-Pt(ii) acceptors into hexagon [6 + 6] or [3 + 3] while the p-conformer only can form smaller polygon cycles. Notably, in contrast with the non-photoactive parallel conformer, the reversible interconversion of anti-parallel ring-open and ring-closed conformer metallacycles can be achieved by alternate irradiation with UV and visible light, respectively, along with a relatively high conversion ratio and good fatigue resistance. This work provides a potential way to construct smart materials for use in sensing, catalysis and drug delivery systems.

Hybrid cis/trans Tetra-arylethenes with Switchable Aggregation-Induced Emission (AIE) and Reversible Photochromism in the Solution, PMMA Film, Solid Powder, and Single Crystal.

How to efficiently design and synthesize multifunctional molecules is particularly challenging. In this presentation, we devote to constructing a kind of simple structures with composite functionalities through straightforward preparation. Starting from common commercially available materials, the titled cis/trans-tetraarylethenes can be conveniently obtained by a one-pot process under mild conditions. The different configurations were confirmed by 1H NMR and single crystal data analysis. The trans-tetraarylethenes could be converted into cis-forms not only by photoirradiation but also by microwave irradiation, which provided us a new choice for isomeric conversion, especially in relation to light sensitivity. Results show that all the hybrid cis/trans-isomers performed switchable fluorescence and reversible photochromism in solution, PMMA film, solid powder, and single crystal. Moreover, these hybrid tetraarylethenes could be utilized as photoswitchable media to tune the behavior of aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ). These versatile properties are favorable for the potential applications in fluorescent photoswitches, nondestructive readout, and logic gates. We hope that our design strategy could provide a new protocol for constructing a kind of multifunctional molecules based some simple structure and convenient synthetic procedures.

Unexpected Interactions between Alkyl Straps and Pyridine Ligands in Sulfur-Strapped Porphyrin Nanorings.

Strapped or "basket-handle" porphyrins have been investigated previously as hemoglobin mimics and catalysts. The facial selectivity of their interactions with axial ligands is a sensitive test for noncovalent bonding. Here the binding of pyridyl ligands to zinc porphyrins with thioester-linked alkyl straps is investigated in solution by NMR spectroscopy and UV-vis titration, and in the solid state by X-ray crystallography. We expected that coordination of the axial ligand would occur on the less hindered face of the porphyrin, away from the strap. Surprisingly, attractive interactions between the strap and the ligand direct axial coordination to the strapped face of the porphyrin, except when the strap is short and tight. The strapped porphyrins were incorporated into π-conjugated cyclic porphyrin hexamers using template-directed synthesis. The strap and the sulfur substituents are located either inside or outside the porphyrin nanoring, depending on the length of the strap. Six-porphyrin nanorings with outwardly pointing sulfur anchors were prepared for exploring quantum interference effects in single-molecule charge transport.

Contribution of glutaredoxin-1 to S-glutathionylation of endothelial nitric oxide synthase for mesenteric nitric oxide generation in experimental necrotizing enterocolitis.

Endothelial nitric oxide synthase (eNOS) is critical for intestinal microcirculatory perfusion and therefore plays a key role in the development of necrotizing enterocolitis (NEC). eNOS-derived nitric oxide (NO) is inhibited by S-glutathionylation of eNOS (eNOS-SSG), which can be reversed by glutaredoxin-1 (Grx1). Therefore, the objective of this study was to investigate the interplay between Grx1 and eNOS in regulating the following inflammation signal during the development of NEC. Primary mouse intestinal microvascular endothelial cells (MIMECs) and peritoneal macrophages were subjected to lipopolysaccharide treatment, and Grx1-/- mice were subjected to an NEC-inducing regimen of formula feeding in combination with hypoxia and hypothermia. The eNOS-SSG level and its activity were assessed using immunoprecipitated assay and NO production evaluation. NO-mediated Toll-like receptor 4 (TLR4) signaling and inflammation injury were further defined. NEC severity was significantly increased in Grx1-/- mice. Grx1-/- mice with NEC showed significantly decreased NO and increased O2•- production with increases in eNOS-SSG. Furthermore, TLR4 signaling, which is required for the development of NEC, was enhanced in the Grx1-deficient mice. These results suggest that eNOS-SSG within the MIMECs inhibited NO production and enhanced TLR4 activity, which were implicated in the pathogenesis of NEC. Grx1 deficiency increases the severity of NEC in association with eNOS-SSG.

Disease progression of acute pancreatitis in pediatric patients.

BACKGROUND: Approximately 10% of patients with acute pancreatitis (AP) progress to chronic pancreatitis. Little is known about the factors that affect recurrence of pancreatitis after an initial episode. We retrospectively investigated patients with AP, focusing on their outcomes and the predictors for disease progression. METHODS: Between July 2003 and June 2015, we retrospectively enrolled first-time AP patients with medical records on disease etiology, severity (according to the Atlanta classifications), and recurrence of AP. Independent predictors of recurrent AP (RAP) and chronic pancreatitis were identified using the logistic regression model. RESULTS: Of the total 159 patients, 45 (28.3%) developed RAP, including two episodes of RAP in 19 patients, and 9 (5.7%) developed chronic pancreatitis. The median duration from the time of AP to the onset of RAP was 5.6 ± 2.3 months. RAP patients were identified as more common among patients with idiopathic first-time AP. The presence of severe ascites, pancreatic necrosis, and systemic complications was independent predictors of RAP in pediatric patients. Experiencing over two RAP episodes was the predictor for developing chronic pancreatitis. No influence of age or number of AP episodes was found on the occurrence of abdominal pain, pain severity, and the prevalence of any pain. CONCLUSIONS: Severity of first-time AP and idiopathic first-time AP are related to RAP. Recurrence increases risk for progression to chronic pancreatitis. The risk of recurrence increased with increasing numbers of AP episodes.

Serum bacterial DNA detection in patients with cholangitis after Kasai procedure.

BACKGROUND: The aim of this study was to investigate the detectability of bacterial DNA (bactDNA) and associated clinical factors in patients with cholangitis after the Kasai procedure through the identification of bactDNA in blood. METHODS: A cross-sectional study of 110 patients who had undergone the Kasai procedure was carried out. A total of 77 patients had cholangitis and 33 did not. Blood samples were obtained on admission or on follow up at the outpatient visit. bactDNA was analyzed using a polymerase chain reaction-based method, DNA nucleotide sequencing, for identification of bacterial species. RESULTS: Rate of bactDNA positivity was higher using the 16SrDNA method than the culture method (58.4% vs 14.3%, P < 0.0001), and more patients with cholangitis were positive for bactDNA compared with the patients without cholangitis (58.4% vs 39.4%, P = 0.095). Bacteria identified on blood 16SrDNA primarily consisted of opportunistic pathogens derived from the gut, including Escherichia coli, Klebsiella pneumoniae, Shigella fexneri, and Enterobacteriaceae bacterium. Treatment with probiotics or antibiotics showed a trend toward reduced prevalence of bactDNA. Pediatric end-stage liver disease score, procalcitonin, C-reactive protein, and heart rate were all significantly associated with the presence of bactDNA. CONCLUSION: bactDNA is frequently detected in patients with cholangitis after the Kasai procedure compared with those without cholangitis (and controls), and the bacteria are similar to those in the gut, suggesting that it is useful as an early diagnostic tool for cholangitis and other infections (registration number in Chinese Clinical Trial Registry ChiCTR-ECC-13003759).

Bim and VDAC1 are hierarchically essential for mitochondrial ATF2 mediated cell death.

BACKGROUND: ATF2 mediated cytochrome c release is the formation of a channel with some unknown factors larger than that of the individual proteins. BHS-only proteins (BH3s), such as Bim, could induce BAX and VDAC, forming a new channel. According to this facts, we can speculated that there is possible signal relationship with BH3s and ATF2, which is associated with mitochondrial-based death programs. METHODS: The growth inhibitory effects of mitochondrial ATF2 were tested in cancer cell lines B16F10, A549, EG7, and LL2. Apoptosis was measured by flow cytometry. The effects of ATF2 and levels of apoptosis regulatory proteins were measured by Western blotting. The interaction of proteins were evaluated by immunoprecipitation analysis. The in vivo antitumor activity of mitochondrial ATF2 were tested in xenograft B16F10 models. RESULTS: Genotoxic stress enabled mitochondrial ATF2 accumulation, perturbing the HK1-VDAC1 complex, increasing mitochondrial permeability, and promoting apoptosis. ATF2 inhibition strongly reduced the conformational activation of Bim, suggesting that Bim acts downstream of ATF2. Although Bim downregulation had no effect on ATF2 activation, Bim knockdown abolished VDAC1 activation; the failure of VDAC1 activation in Bim-depleted cells could be reversed by the BH3-only protein mimic ABT-737. We also demonstrate that silencing of ATF2 in B16F10 cells increases both the incidence and prevalence of tumor xenografts in vivo, whereas stably mitochondrial ATF2 transfection inhibited B16F10 tumor xenografts growth. CONCLUSIONS: Altogether, these results show that ATF2 is a component of the apoptosis machinery that involves a hierarchical contribution of ATF2, Bim, and VDAC1. Our data offer new insight into the mechanism of mitochondrial ATF2 in mitochondrial apoptosis.

Two Stepwise Synthetic Routes toward a Hetero[4]rotaxane.

Heterorotaxanes have been emerging as an important class of mechanically interlocked molecules and have attracted much attention in recent years. Driven by the distinguishable host-guest interactions between crown ether macrocycles and ammonium with different sizes, a novel hetero[4]rotaxane was successfully prepared by employing the combination of copper-catalyzed "click" reaction and P(n-Bu)3-catalyzed esterification reaction as stoppering reactions. The hetero[4]rotaxane contains an interlocked species in which a dibenzo[24]crown-8 ring threaded by a dibenzylammonium-containing component with two benzo[21]crown-7 macrocycles at both ends to act as stoppers, and each of the two benzo[21]crown-7 rings is also threaded with a benzylalkylammonium unit to form the second interlocked species. The hetero[4]rotaxane was prepared through two different stepwise synthetic routes, and the complicated chemical structure of the hetero[4]rotaxane was well-characterized by (1)H NMR spectroscopy and high-resolution electrospray ionization (HR-ESI) mass spectrometry. The investigation shows that the construction of complicated topological heterorotaxane can be achieved via distinct approaches with high efficiencies, which may provide a foundation for the construction of more sophisticated heterorotaxane systems or functional supermolecules.

Effective strategy of the combination of high-intensity focused ultrasound and transarterial chemoembolization for improving outcome of unresectable and metastatic hepatoblastoma: a retrospective cohort study.

The combination of high-intensity focused ultrasound (HIFU) and transarterial chemoembolization (TACE) has been experimentally performed in a variety of malignant tumors, and its validity has not yet been evaluated for hepatoblastoma (HB). We evaluated the disease-response rate, resection rate, and toxicity in children with unresectable or metastatic HB (stage III and stage IV HB) after sequential treatment with TACE plus HIFU in a controlled clinical trial. The 35 patients with unresectable or metastatic HB were nonrandomly assigned to HIFU ablation (n = 12) or C5V chemotherapy (n = 23). The rates of complete resection, tumor response, and treatment toxicity were evaluated for both regimens. Nine patients who received C5V and 10 patients who received TACE plus HIFU became operable (P = .02). The 3-year event-free survival and overall survival rates were 43.03% and 56.68% in the C5V group and 38.57% and 57.86% in the TACE plus HIFU group, respectively. Acute grade 3 or 4 adverse events, including neutropenia, thrombocytopenia, and anemia, were more frequent in patients treated with C5V therapy than in patients receiving TACE plus HIFU. HIFU ablation achieved a higher rate of complete resection and a lower rate of severe complications compared with C5V treatment in children with advanced HB (Chinese Clinical Trials Registry No. ChiCTR-PRCH-08000182).

Facile synthesis and characterization of new photochromic trans-dithienylethenes functionalized with pyridines and fluorenes.

Three symmetrical and unsymmetrical trans-dithienylethenes functionalized with pyridines and fluorenes have been synthesized by a facile one-pot procedure, and their characteristics and photochromism were investigated. Their fluorescent intensity was efficiently regulated by a photochromic switch using alternative irradiation with UV light and visible light. Moreover, by protonation and complexation, the pyridyl-substituted compounds also showed excellent photoswitching properties with distinguishable color changes. These characteristics are expected to be applicable to potential multi-addressable photoswitch and erasable optical data processing technologies.