Phototunable and Photopatternable Polymer Semiconductors.

ConspectusIn recent decades, there has been rapid development in the field of polymer semiconductors, particularly those based on conjugated donor-acceptor (D-A) polymers exhibiting high charge mobilities. Furthermore, the application of polymer semiconductors has been successfully extended to a wide range of functional devices, including sensors, photodetectors, radio frequency identification (RFID) tags, electronic paper, skin electronics, and artificial synapses. Over the past few years, there has been a growing focus on stimuli-responsive polymer semiconductors, which have the potential to impart additional functionalities to conventional field-effect transistors, garnering increased attention within the research community. In this context, phototunable polymer semiconductors have received significant attention due to their ability to utilize light as an external stimulus, enabling remote control of device performance with high spatiotemporal resolution. Meanwhile, integration of field-effect transistors with polymer semiconductors can enable the realization of complex functions. To achieve this, precise and controllable patterning of polymer semiconductors becomes essential. In this Account, we discuss our research findings in the context of phototunable and photopatternable polymer semiconductors. These developments encompass the following key aspects: (i) polymer semiconductors, such as poly(diketopyrrolopyrrole-quaterthiophene) (PDPP4T), exhibit phototunability when blended with the photochromic compound hexaarylbiimidazole (HABI). The photo/thermal-responsive field-effect transistors (FETs) can be fabricated using blending thin films. Remarkably, these photo/thermal-responsive transistors can function as photonically programmable and thermally erasable nonvolatile memory devices. (ii) By incorporating photoswitchable groups like azo and spiropyran into the side chains of conjugated D-A polymers, we can create phototunable polymer semiconductors. The reversible isomerization of azo and spiropyran groups significantly influences the charge transport properties of these polymer semiconductors. Consequently, the performance of the resulting FETs can be reversibly tuned through UV/visible or near-infrared light (NIR) irradiation. Notably, the incorporation of two distinct azo groups into the side chains leads to polymer semiconductors with tristable semiconducting states, offering the ability to logically control device performance using light irradiation at three different wavelengths. (iii) Photopatterning of p-type, n-type, and ambipolar semiconductors featuring alkyl side chains can be achieved using a diazirine-based, four-armed photo-cross-linker (4CNN) with a loading concentration of no more than 3% (w/w). Furthermore, the semiconducting performances of FETs with patterned thin films were found to be satisfactorily uniform. Importantly, the cross-linked thin films are robust and show good resistance to organic solvents, which is useful for fabricating all-solution processable multilayer electronic devices. (iv) The introduction of azide groups into the side chains of conjugated polymers results in a single-component semiconducting photoresist. The presence of azide groups renders the side chains with photo-cross-linking ability, enabling the successful formation of uniform patterns, even as small as 5 µm, under UV light irradiation. Benefiting from the single component feature, field-effect transistors with individual patterned thin films display satisfactorily uniform performances. Moreover, this semiconducting photoresist has proven effective for efficiently photopatterning other polymer semiconductors, demonstrating its versatility.

NDRG1 Signaling Is Essential for Endothelial Inflammation and Vascular Remodeling.

BACKGROUND: NDRG-1 (N-myc downstream-regulated gene 1) is a member of NDRG family that plays essential roles in cell differentiation, proliferation, and stress responses. Although the expression of NDRG1 is regulated by fluid shear stress, its roles in vascular biology remain poorly understood. The purpose of the study is to determine the functional significance of NDRG1 in vascular inflammation and remodeling. METHODS AND RESULTS: By using quantitative polymerase chain reaction, western blot, and immunohistochemistry, we demonstrate that the expression of NDRG1 is markedly increased in cytokine-stimulated endothelial cells and in human and mouse atherosclerotic lesions. To determine the role of NDRG1 in endothelial activation, we performed loss-of-function studies using NDRG1 short hairpin RNA. Our results demonstrate that NDRG1 knockdown by lentivirus bearing NDRG1 short hairpin RNA substantially attenuates both IL-1ß (interleukin-1ß) and TNF-α (tumor necrosis factor-α)-induced expression of cytokines/chemokines and adhesion molecules. Intriguingly, inhibition of NDRG1 also significantly attenuates the expression of procoagulant molecules, such as PAI-1 (plasminogen activator inhibitor type 1) and TF (tissue factor), and increases the expression of TM (thrombomodulin) and t-PA (tissue-type plasminogen activator), thus exerting potent antithrombotic effects in endothelial cells. Mechanistically, we showed that NDRG1 interacts with orphan Nur77 (nuclear receptor) and functionally inhibits the transcriptional activity of Nur77 and NF-κB (nuclear factor Kappa B) in endothelial cells. Moreover, in NDRG1 knockdown cells, both cytokine-induced mitogen-activated protein kinase activation, c-Jun phosphorylation, and AP-1 (activator protein 1) transcriptional activity are substantially inhibited. Neointima and atherosclerosis formation induced by carotid artery ligation and arterial thrombosis were markedly attenuated in endothelial cell-specific NDRG1 knockout mice compared with their wild-type littermates. CONCLUSIONS: Our results for the first time identify NDRG1 as a critical mediator implicated in regulating endothelial inflammation, thrombotic responses, and vascular remodeling, and suggest that inhibition of NDRG1 may represent a novel therapeutic strategy for inflammatory vascular diseases, such as atherothrombosis and restenosis.

Axially Chiral Nonbenzenoid Nanographene with Second Harmonic Generation Property.

Chiral nanographenes (NGs) have garnered significant interest as optoelectronic materials in recent years. While helically chiral NGs have been extensively studied, axially chiral NGs have only witnessed limited examples, with no prior reports of axially chiral nonbenzenoid NGs. Herein we report an axially chiral nonbenzenoid nanographene featuring six pentagons and four heptagons. This compound, denoted as 2, was efficiently synthesized via an efficient Pd-catalyzed aryl silane homocoupling reaction. The presence of two bulky 3,5-di-tert-butylphenyl groups around the axis connecting the two nonbenzenoid PAH (AHR) segments endows 2 with atropisomeric chirality and high racemization energy barrier, effectively preventing racemization of both R- and S-enantiomers at room temperature. Optically pure R-2 and S-2 were obtained by chiral HPLC separation, and they exhibit circular dichroism (CD) activity at wavelengths up to 660 nm, one of the longest wavelengths with CD responses reported for the chiral NGs. Interestingly, racemic 2 forms a homoconfiguration π-dimer in the crystal lattice, belonging to the I222 chiral space group. Consequently, this unique structure renders crystals of 2 with a second harmonic generation (SHG) response, distinguishing it from all the reported axially chiral benzenoid NGs. Moreover, R-2 and S-2 also exhibit SHG-CD properties.

Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT gene.

OBJECTIVE: Calcific aortic valve disease (CAVD) is the leading cause of angina, heart failure, and death from aortic stenosis. However, the molecular mechanisms of its progression, especially the complex disease-related transcriptional regulatory mechanisms, remain to be further elucidated. METHODS: This study used porcine valvular interstitial cells (PVIC) as a model. We used osteogenic induced medium (OIM) to induce calcium deposition in PVICs to calcify them, followed by basic fibroblast growth factor (bFGF) treatment to inhibit calcium deposition. Transcriptome sequencing was used to study the mRNA expression profile of PVICs and its related transcriptional regulation. We used DaPars to further examine alternative polyadenylation (APA) between different treatment groups. RESULTS: We successfully induced calcium deposition of PVICs through OIM. Subsequently, mRNA-seq was used to identify differentially expressed mRNAs for three different treatments: control, OIM-induced and OIM-induced bFGF treatment. Global APA events were identified in the OIM and bFGF treatment groups by bioinformatics analysis. Finally, it was discovered and proven that catalase (CAT) is one of the potential targets of bFGF-induced APA regulation. CONCLUSION: We described a global APA change in a calcium deposition model related to CAVD. We revealed that transcriptional regulation of the CAT gene may contribute to bFGF-induced calcium deposition inhibition.

Moho Imaging with Fiber Borehole Strainmeters Based on Ambient Noise Autocorrelation.

Moho tomography is important for studying the deep Earth structure and geodynamics, and fiber borehole strainmeters are broadband, low-noise, and attractive tools for seismic observation. Recently, many studies have shown that fiber optic seismic sensors can be used for subsurface structure imaging based on ambient noise cross-correlation, similar to conventional geophones. However, this array-dependent cross-correlation method is not suitable for fiber borehole strainmeters. Here, we developed a Moho imaging scheme for the characteristics of fiber borehole strainmeters based on ambient noise autocorrelation. S-wave reflection signals were extracted from the ambient noise through a series of processing steps, including phase autocorrelation (PAC), phase-weighted stacking (PWS), etc. Subsequently, the time-to-depth conversion crustal thickness beneath the station was calculated. We applied our scheme to continuous four-component recordings from four fiber borehole strainmeters in Lu'an, Anhui Province, China. The obtained Moho depth was consistent with the previous research results. Our work shows that this method is suitable for Moho imaging with fiber borehole strainmeters without relying on the number of stations.

Tetraphenylethene-Based cis/trans Isomers for Targeted Fluorescence Sensing and Biomedical Applications.

Molecular probes which can be modulated, functionalized and used to visualize the processes are highly desirable for understanding and manipulating biological systems. Geometric cis and trans isomers of tetraphenylethene (TPE) emerge as attractive candidates to fulfill these tasks thanks to the unique aggregation-induced emission properties, tailorable structures, and responsiveness to external stimuli. This minireview focuses on cis and trans isomers of TPE derivatives that are functionalized with molecular recognition units for fluorescence detection, bioimaging and cancer therapy. The effects of molecular geometry on fluorescence property, target binding ability and biological activity are summarized. The feasibility to in vitro and in vivo switch molecular configuration and thus bio-activity is discussed. Finally, the future development and challenges are discussed in view of TPE-based stereoisomers for targeted sensing and imaging-guided modulation of biological processes.

GRPAFusion: A Gradient Residual and Pyramid Attention-Based Multiscale Network for Multimodal Image Fusion.

Multimodal image fusion aims to retain valid information from different modalities, remove redundant information to highlight critical targets, and maintain rich texture details in the fused image. However, current image fusion networks only use simple convolutional layers to extract features, ignoring global dependencies and channel contexts. This paper proposes GRPAFusion, a multimodal image fusion framework based on gradient residual and pyramid attention. The framework uses multiscale gradient residual blocks to extract multiscale structural features and multigranularity detail features from the source image. The depth features from different modalities were adaptively corrected for inter-channel responses using a pyramid split attention module to generate high-quality fused images. Experimental results on public datasets indicated that GRPAFusion outperforms the current fusion methods in subjective and objective evaluations.

A Heptacene Analogue Entailing a Quinoidal Benzodi[7]annulene (7/6/7 Ring) Core with a Tunable Configuration and Multiple Redox Properties.

Non-benzenoid acenes containing heptagons have received increasing attention. We herein report a heptacene analogue containing a quinoidal benzodi[7]annulene core. Derivatives of this new non-benzenoid acene were obtained through an efficient synthetic strategy involving an Aldol condensation and a Diels-Alder reaction as key steps. The configuration of this heptacene analogue can be modulated from a wavy to a curved one by just varying the substituents from a (triisopropylsilyl)ethynyl group to a 2,4,6-triisopropylphenyl (Trip) group. When mesityl (Mes) groups are linked to the heptagons, the resulting non-benzenoid acene displays polymorphism with a tunable configuration from a curved to a wavy one upon varying the crystallization conditions. In addition, this new non-benzenoid acene can be oxidized or reduced by NOSbF6 or KC8 to the respective radical cation or radical anion. Compared with the neutral acene, the radical anion shows a wavy configuration and the central hexagon becomes aromatic.

Diazulenorubicene as a Non-benzenoid Isomer of peri-Tetracene with Two Sets of 5/7/5 Membered Rings Showing Good Semiconducting Properties.

Non-benzenoid polycyclic aromatic hydrocarbons (PAHs) have received a lot of attention because of their unique optical, electronic, and magnetic properties, but their synthesis remains challenging. Herein, we report a non-benzenoid isomer of peri-tetracene, diazulenorubicene (DAR), with two sets of 5/7/5 membered rings synthesized by a (3+2) annulation reaction. Compared with the precursor containing only 5/7 membered rings, the newly formed five membered rings switch the aromaticity of the original heptagon/pentagon from antiaromatic/aromatic to non-aromatic/antiaromatic respectively, modify the intermolecular packing modes, and lower the LUMO levels. Notably, compound 2 b (DAR-TMS) shows p-type semiconducting properties with a hole mobility up to 1.27 cm2  V-1 s-1 . Moreover, further extension to larger non-benzenoid PAHs with 19 rings was achieved through on-surface chemistry from the DAR derivative with one alkynyl group.

Single-cell transcriptomic analysis reveals differential cell subpopulations and distinct phenotype transition in normal and dissected ascending aorta.

BACKGROUND: Acute thoracic aortic dissection (ATAD) is a fatal condition characterized by tear of intima, formation of false lumen and rupture of aorta. However, the subpopulations of normal and dissected aorta remain less studied. METHODS: Single-cell RNA sequencing was performed including 5 patients with ATAD and 4 healthy controls. Immunohistochemistry and immunofluorescence were used to verify the findings. RESULTS: We got 8 cell types from human ascending aorta and identified 50 subpopulations including vascular smooth muscle cells (VSMCs), endothelial cells, fibroblasts, neutrophils, monocytes and macrophages. Six transmembrane epithelial antigen of prostate 4 metalloreductase (STEAP4) was identified as a new marker of synthetic VSMCs. CytoTRACE identified subpopulations with higher differentiation potential in specified cell types including synthetic VSMCs, enolase 1+ fibroblasts and myeloid-derived neutrophils. Synthetic VSMCs-derived C-X-C motif chemokine ligand 12 (CXCL12) might interact with neutrophils and fibroblasts via C-X-C motif chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), respectively, which might recruit neutrophils and induce transdifferentitation of fibroblasts into synthetic VSMCs. CONCLUSION: We characterized signatures of different cell types in normal and dissected human ascending aorta and identified a new marker for isolation of synthetic VSMCs. Moreover, we proposed a potential mechanism that synthetic VSMCs might interact with neutrophils and fibroblasts via CXCL12-CXCR4/ACKR3 axis whereby deteriorating the progression of ATAD, which might provide new insights to better understand the development and progression of ATAD.

An Analysis of Total Arch Re-Replacement After Proximal Aortic Surgery.

BACKGROUND: After proximal aortic surgery, total arch replacement (TAR) may again be needed because of recurrent dissection or aneurysm. This paper analyzed the relevant data of this technology with hopes of improving cognition and treatment. METHODS: There were a total of 60 eligible cases of secondary TAR after proximal aortic surgery in our center from 2010 to 2020. The primary surgical procedures included aortic valve replacement (AVR), ascending aortic replacement, Bentall, hemi-arch replacement, and thoracic endovascular aortic repair (TEVAR). The data were analyzed using the IBM SPSS Statistics 23.0 for Windows™ and presented as the mean ± standard deviations and direct frequencies, as appropriate. RESULTS: The interval between two operations was 44.8±53.6 months, 24 cases (40%) underwent emergency operation, the recurrence of type A dissection included 51 cases, accounting for 85% of the causes of total arch re-replacement. In the second surgical procedures, the ascending + TAR + stented elephant trunk (SET) implantation accounted for 75.0%. The overall surgical success rate was 98.3%. Postoperative respiratory complications were the most common, including infection, pneumothorax and hemothorax in 21 cases (35.6%). The second most common complication was acute kidney injury (AKI) in six cases (10.2%), and neurological complications took place in three cases (5.1%). The 30-day mortality rate was 15.3% and the 1-, 3- and 5-year survival rates were 96.0%, 84.0%, and 76.0%, respectively. CONCLUSIONS: The recurrence of dissection is the main cause of TAR after proximal aortic surgery, followed by aneurysm and the resurgical criteria for aneurysm needs to be unified. In addition to TAR, SET also is widely used. Despite high early mortality, its long-term prognosis is acceptable.

Tuning Proapoptotic Activity of a Phosphoric-Acid-Tethered Tetraphenylethene by Visible-Light-Triggered Isomerization and Switchable Protein Interactions for Cancer Therapy.

We herein report a phosphoric-acid-substituted tetraphenylethene (T-P) capable of adapting its geometric configuration and biological activity to the microenvironment upon light irradiation for apoptosis modulation. Different from most ultraviolet-responsive isomerization, T-P undergoes cis-trans isomerization under visible light irradiation, which is biocompatible and thus photo-modulation is possible in living biosystems. By using alkaline phosphatase (ALP) and albumin as dual targets, T-P isomers display different protein binding selectivity, cancer-cell internalization efficiency and apoptosis-inducing ability. The proapoptotic activity was found to be kinetically controlled by the enzymatic reaction with ALP and regulated by co-existing albumin. Motivated by these findings, two-way modulation of proapoptotic effect and on-demand boosting anticancer efficacy were realized in vitro and in vivo using light and endogenous proteins as multiple non-invasive switching stimuli.

Single-Molecule Charge-Transport Modulation Induced by Steric Effects of Side Alkyl Chains.

The experimental investigation of side-chain effects on intramolecular charge transport in π-conjugated molecules is essential but remains challenging. Herein, the dependence of intra-molecular conductance on the nature of branching alkyl chains is investigated through a combination of the scanning tunneling microscope break junction (STM-BJ) technique and density functional theory. Three thiophene-flanked diketopyrrolopyrrole (DPP) derivatives with different branching alkyl chains (isopentane, 3-methylheptane, and 9-methylnonadecane) are used with phenylthiomethyl groups as the anchoring groups. The results of single-molecule conductance measurements show that as the alkyl chain becomes longer, the torsional angles between the aromatic rings increase due to steric crowding, and therefore, the molecular conductance of DPP decreases due to reduction in conjugation. Both theoretical simulations and 1 H NMR spectra demonstrate that the planarity of the DPPs is directly reduced after introducing longer branching alkyl chains, which leads to a reduced conductance. This work indicates that the effect of the insulating side chain on the single-molecule conductance cannot be neglected, which should be considered for the design of future organic semiconducting materials.

Clinical Outcome of Reoperation for Mechanical Prosthesis at Aortic Position.

AIM: Redo aortic valve surgery is usually associated with a high risk of mortality and complications. The aim of this study was to investigate the perioperative and long-term outcomes of reoperation after prior mechanical prosthesis implantation at the aortic position. METHOD: The clinical data of 146 consecutive patients who underwent reoperation at the aortic position between 2003 and 2019 were analysed. RESULTS: Mean age was 51.5±12.7 years and 69 (47.3%) were female. The median interval from prior surgery to redo aortic valve surgery was 6 years. The aetiologies were pannus formation with prosthetic aortic stenosis in 62 cases (42.5%), prosthetic valve endocarditis (PVE) in five (3.4%), PVE with perivalvular leakage (PVL) in 16 (11.0%), PVL in 45 (30.8%), thrombosis in seven (4.8%), and aortic disease in 11 (7.5%). As for surgical procedure, aortic valve replacement was performed in 81 cases (55.5%), Bentall in 34 (23.3%), PVL repair in six (4.1%), and pannus debridement in 25 (17.1%). Fourteen (14) (9.6%) patients expired perioperatively. Prolonged ventilation time and postoperative renal failure were proved to be significant independent predictors of mortality according to multivariate analysis. Overall survival was 87.8%±7.4% and 76.4%±15.1% at 5 and 10 years, respectively. Survival was 87.7%±13.7% and 84.2%±15.6% in the pannus group, and 84.5%±12.6% and 74.6%±19.4% in the non-pannus group at 5 and 10 years, respectively (p=0.951). Survival was 87.5%±14.2% and 75.8%±22.7% in the PVL group and 84.7%±11.9% and 81.6%±13.5% in the non-PVL group at 5 and 10 years, respectively (p=0.365). CONCLUSIONS: Pannus formation and PVL are two major indications for reoperation of mechanical prosthesis at the aortic position. Redo aortic valve surgery has a satisfactory outcome but with a high risk of complications. Long-term survival of patients seems not to be related to the aetiology. Final decision-making of redo aortic valve surgery should be based on aetiology.

An Efficient Diazirine-Based Four-Armed Cross-linker for Photo-patterning of Polymeric Semiconductors.

A diazirine-based four-armed cross-linker (4CNN) with a tetrahedron geometry is presented for efficient patterning of polymeric semiconductors by photo-induced carbene insertion. After blending of 4CNN with no more than 3 % (w/w), photo-patterning of p-, n-, and ambipolar semiconducting polymers with side alkyl chains was achieved; regular patterns with size as small as 5 µm were prepared with appropriate photomasks after 365 nm irradiation for just 40 s. The interchain packing order and the thin film morphology were nearly unaltered after the cross-linking and the semiconducting properties of the patterned thin films were mostly retained. A complementary-like inverter with a gain value of 112 was constructed easily by two steps of photo-patterning of the p-type and n-type semiconducting polymers. The results show that 4CNN is a new generation of cross-linker for the photo-patterning of polymeric semiconductors for all-solution-processible flexible electronic devices.

New Synthetic Approaches to N-Aryl and π-Expanded Diketopyrrolopyrroles as New Building Blocks for Organic Optoelectronic Materials.

Diketopyrrolopyrrole (DPP) as a building block has been intensively investigated for organic semiconductors and light emitting materials. The synthesis of N-aryl DPPs remains challenging. Herein, we firstly report a new easily handled synthetic method toward N-aryl DPPs through H-DPP with diaryliodonium salt in the presence of CuI, which shows broad reaction scope. Sixteen N-aryl DPPs, including phenyl, furan and thiophene as flanking aromatic groups, were synthesized with yields up to 78 %. These N-aryl DPPs are fluorescent in both solutions and solid states, with quantum yields up to 96 % and 40 %, respectively. Moreover, we show that the reaction between H-DPP and diaryliodonium salt can lead to π-expanded DPPs by using Pd(OAc)2 as catalyst. Nine π-expanded DPPs were obtained in 27-61 % yields. These π-expanded DPPs exhibit good semiconducting properties with hole mobility of 0.71 cm2 V-1 s-1 , demonstrating that they are useful building blocks for high performance organic semiconductors.

Pyridinium-Substituted Tetraphenylethylenes Functionalized with Alkyl Chains as Autophagy Modulators for Cancer Therapy.

Tuning autophagy in a controlled manner could facilitate cancer therapy but it remains challenging. Pyridinium-substituted tetraphenylethylene salts (PTPE 1-3), able to target mitochondria and disrupt autophagy after forming complexes with albumin, are reported. Mitochondrion affinity and autophagy-inducing activity are improved by prolonging the length of alkyl chains in PTPE 1-3. PTPE 1-3 demonstrate proautophagic activity and a mitophagy blockage effect. Failure of autophagosome-lysosome fusion in downstream autophagy flux results in cancer cell death. Moreover, fast formation of complexes of PTPE 1-3 with albumin in blood can facilitate biomimetic delivery and deep tumor penetration. Efficient tumor accumulation and effective tumor suppression are successfully demonstrated with in vitro and in vivo studies. PTPE 1-3 salts exhibit dual functionality: they target and image mitochondria because of aggregation-induced emission effects and they are promising for cancer therapy.

A Conjugated Polymer Containing Arylazopyrazole Units in the Side Chains for Field-Effect Transistors Optically Tunable by Near Infra-Red Light.

Optically tunable field-effect transistors (FETs) with near infra-red (NIR) light show promising applications in various areas. Now, arylazopyrazole groups are incorporated in the side chains of a semiconducting donor-acceptor (D-A) polymer. The cis-trans interconversion of the arylazopyrazole can be controlled by 980 nm and 808 nm NIR light irradiation, by utilizing NaYF4 :Yb,Tm upconversion nanoparticles and the photothermal effect of conjugated D-A polymers, respectively. This reversible transformation affects the interchain packing of the polymer thin film, which in turn reversibly tunes the semiconducting properties of the FETs by the successive 980 nm and 808 nm light irradiation. The resultant FETs display fast response to NIR light, good resistance to photofatigue, and stability in storage for up to 120 days. These unique features will be useful in future memory and bioelectronic wearable devices.

Dicyclohepta[ijkl,uvwx]rubicene with Two Pentagons and Two Heptagons as a Stable and Planar Non-benzenoid Nanographene.

Polycyclic aromatic hydrocarbons with hexagons/pentagons or hexagons/heptagons have been intensively investigated in recent years, but those with simultaneous presence of hexagons, pentagons and heptagons remain rare. In this paper, we report dicyclohepta[ijkl,uvwx]rubicene (DHR), a non-benzenoid isomer of dibenzo[bc,kl]coronene with two pentagons and two heptagons. We developed an efficient and scalable synthetic method for DHR by using Scholl reaction and dehydrogenation. Crystal structure of DHR shows that the benzenoid rings, two pentagons and two heptagons are coplanar. The bond lengths analysis and the ICSS(1)zz and LOL-π calculations indicate that the incorporation of two formal azulene moieties has an effect on the conjugated structure. The π-electrons of benzenoid and pentagon rings are more delocalized. Cyclic voltammetry studies indicate that DHR shows multiple oxidation and reduction potentials. Interestingly, DHR exhibits unusual S0 to S2 absorption and abnormal anti-Kasha S2 to S0 emission. Moreover, crystals of DHR exhibit semiconducting behaviour with hole mobility up to 0.082 cm2 V-1 s-1 .

Nur77 limits endothelial barrier disruption to LPS in the mouse lung.

Nur77 is an orphan nuclear receptor implicated in the regulation of a wide range of biological processes, including the maintenance of systemic blood vessel homeostasis. Although Nur77 is known to be expressed in the lung, its role in regulating pulmonary vascular functions remains entirely unknown. In this study, we found that Nur77 is expressed at high levels in the lung, and its expression is markedly upregulated in response to LPS administration. While the pulmonary vasculature of mice that lacked Nur77 appeared to function normally under homeostatic conditions, we observed a dramatic decrease in its barrier functions after exposure to LPS, as demonstrated by an increase in serum proteins in the bronchoalveolar lavage fluid and a reduction in the expression of endothelial junctional proteins, such as vascular endothelial cadherin (VE-cadherin) and ß-catenin. Similarly, we found that siRNA knockdown of Nur77 in lung microvascular endothelial cells also reduced VE-cadherin and ß-catenin expression and increased the quantity of fluorescein isothiocyanate-labeled dextran transporting across LPS-injured endothelial monolayers. Consistent with Nur77 playing a vascular protective role, we found that adenoviral-mediated overexpression of Nur77 both enhanced expression of VE-cadherin and ß-catenin and augmented endothelial barrier protection to LPS in cultured cells. Mechanistically, Nur77 appeared to mediate its protective effects, at least in part, by binding to ß-catenin and preventing its degradation. Our findings demonstrate a key role for Nur77 in the maintenance of lung endothelial barrier protection to LPS and suggest that therapeutic strategies aimed at augmenting Nur77 levels might be effective in treating a wide variety of inflammatory vascular diseases of the lung.