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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-1β (interleukin-1β) 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.

A NIR strong absorbing molecule was constructed by taking the structural advantages of a quinoid and diketopyrrolopyrrole, with an absorption maximum of up to 1039 nm and hole and electron mobilities up to 0.19 and 0.2 cm2 V−1 s−1, respectively.

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.

New semiconducting D–A molecules with a fused tetrathiafulvalene–naphthalene diimide framework show near-infrared absorptions and emissions with maxima up to 1062 nm and quantum yields up to 1.64%.

Objective Calcific aortic valve disease (CAVD) is a major cause of aortic stenosis resulting in angina, heart failure, and death. However, the molecular mechanism of its progression, especially the sophisticated disease-related transcriptional regulation machinery remains to be further elucidated. Methods This study was modeled on porcine valvular interstitial cells (PVIC). We used OIM to induce calcification and bFGF treatment to inhibit calcification. The mRNA expression profile of PVICs and their related transcriptional regulation were investigated using transcriptome sequencing. We used DaPars to further examine alternative polyadenylation (APA) among the different treatment groups. Results We identified global APA alteration in the OIM, OIM-bFGF, and Ctrl treatment groups. We also identified the CAT gene as one of the crucial candidate genes that may contribute to calcification inhibition through APA regulation. The alteration of both APA and protein levels of the CAT gene in the bFGF-treated group was further validated using qRT-PCR and western blotting analysis. Conclusion We described a global APA change in a calcification model related to CAVD. We revealed that transcriptional regulation of the CAT gene may contribute to bFGF-induced calcification inhibition.

The soft nature has endowed conjugated polymers with promising applications in a wide range of field‐effect transistor (FET) based flexible electronics. With unremitting efforts on revealing the molecular structure–property relationships, numerous novel conjugated polymers with high mobility and excellent mechanical property have been developed in the past decades. Incorporating hydrogen‐bonding (H‐bonding) units into semiconducting polymers is one of the most successful strategies for designing high‐performance semiconducting materials. In this review, we aim to highlight the roles of H‐bonding units in the performances of polymeric FETs from three aspects. These include (i) charge mobility enhancement for semiconducting polymers after incorporation of H‐bonding units into the side chains, (ii) the effects of H‐bonding units on the stretchability of conjugated polymers, and (iii) the improvement of self‐healing properties of conjugated polymers containing dynamic hydrogen bonds due to the H‐bonding units in the side chains or conjugated backbones.

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.

Diketopyrrolopyrrole (DPP) and its derivatives are commercially used dyes that have drawn great attention in recent years for applications in organic electronic/optical materials. These material studies cannot progress without further developments in the syntheses of the DPP family of molecules. In this review, recent progress in the syntheses of DPP derivatives is summarized in detail as well as the structure–property relationships of the derivatives, including the syntheses of DPP cores, N-functionalization reactions, and π-extensions on and along the DPP cores. Finally, existing problems and future perspectives of DPP-based derivatives are also discussed.

A perylene five-membered ring diimide, PDI39, was developed as a new electron-deficient building block for n-type semiconductors. The π-expanded conjugated molecules containing azulenes were synthesized from PDI39. These conjugated molecules show helical geometry and near-infrared absorption up to 810 nm.

The importance of mitochondria in tumorigenesis makes these organelles an ideal target for cancer therapy. In recent years, luminogens with the aggregation-induced emission (AIE) effect have been developed for mitochondrial targeting and cancer treatment. The induction of mitochondrial dysfunction can be an effective pathway of chemotherapy, photodynamic therapy, and combination therapy against cancer. This review focuses on recent progress in the field of AIE luminogens (AIEgens) for cancer theranostics based on mitochondrial targeting and dysfunction. AIEgens for cancer treatment, including chemotherapy, photodynamic therapy, and combination therapy, are summarized herein. Molecular design efforts toward mitochondrial targeting and mitochondria-damaging mechanisms are also discussed. Finally, we discuss the challenges and future directions of development for AIEgens in mitochondria-targeted cancer treatment.

The diallene-containing compound dACl-1 was unexpectedly obtained by the unconventional transformation of two carbonyl groups in 4,4′,5,5′-tetrachloro-10H,10′H-[9,9′-bianthracenylidene]-10,10′-dion...

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.

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.

Multi-stimuli-responsive field-effect transistors (FETs) with organic/polymeric semiconductors have received increasing attention. Herein, we report a novel strategy for fabricating multi-stimuli-r...

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 .

Organic and organometallic π-conjugated molecules with inherent nonlinear optical (NLO) responses have attracted great interest due to their controllable properties via rational structure modifications. However, most of the state-of-the-art materials such as porphyrins, phthalocyanines, and diacetylenes exhibit NLO responses at visible-light regions. Recently, diketopyrrolopyrrole (DPP) based donor–acceptor (D–A) type π-conjugated copolymers have been found to exhibit NLO responses which can reach up to 1064 nm. However, the design rationality of the structure toward NLO properties is not well understood. Herein, four alternating DPP-based copolymers are constructed by using the electron donors of 2-phenylpyridine for P1, 2-thienylpyridine for P2 and their Pt(II)-incorporated moieties for P1Pt and P2Pt. All copolymers display intense intramolecular charge transfer (ICT) processes, and the ICT absorption can be extended to the near-infrared (NIR) region due to the strong D–A interaction of the π-conjugated backbone. The variation tendency of optical bandgaps estimated from the onset of ICT absorption is P1 (1.60 eV) > P1Pt (1.56 eV) > P2 (1.47 eV) > P2Pt (1.44 eV). Open- and closed-aperture Z-scan experiments disclosed that all copolymers exhibit broadband (532 and 1064 nm) NLO properties due to the synergistic effect of excited state absorption and the ICT process upon excitation of 8 ns as well as 25 ps laser pulses. Pt(II)-incorporation can promote or switch the NLO properties due to the efficient triplet-state absorption introduced by the heavy-atom effect. The improvement of the NLO properties is of the order P1 < P1Pt < P2 < P2Pt, which is consistent with the decreasing trend of the copolymer bandgaps. These results will provide guidelines for the rational design of materials toward broadband NLO responses and advanced applications.

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.

Photodynamic therapy (PDT) has emerged as an attractive alternative in cancer therapy, but therapeutic effects suffer from low photosensitizing efficiency and poor retention of photosensitizes in cancer cells. This paper reports the photosensitizers which show absorption and emission in the long-wavelength region and high photosensitizing efficiency can be formed in situ in cells from 4,6-dibromothieno[3,4-b]thiophene derivative (TT-5-P) after white light irradiation. The self-oligomerization of TT-5-P is uptaken in cells upon light irradiation-induced cell apoptosis simultaneously and efficiently. In addition, the formation of oligomers (TT-5-Ps) enhances the retention time in cells remarkably, which is advantageous for boosting the photodynamic therapy efficiency. Moreover, the selectivity toward tumor cells of TT-5-P can be improved obviously via the formation of complex of TT-5-P with albumin. This in situ photoinduced self-oligomerization strategy can be utilized to design effective biomaterials for long-term imaging and improved therapy.

Organic nonlinear optical (NLO) materials have attracted immense scientific interest in various fields. Broadband NLO response extending to near-infrared (NIR) region is extremely important and remains challenging. Herein, two diketopyrrolopyrrole (DPP)-based donor-acceptor (D-A)-type π-conjugated copolymers with and without Pt(II) incorporation are rationally designed and synthesized toward broadband NLO response materials. The broad intramolecular charge transfer (ICT) absorption reaching 1000 nm due to the strong D-A interaction is well demonstrated by photophysical characterizations. The NLO properties of copolymers are studied using Z-scan technology. Owing to their extended π-conjugated D-A systems and near-infrared ICT absorption properties, both copolymers exhibit laser-induced NLO response to nanosecond as well as picosecond laser pulses upon the wavelengths of 532 and 1064 nm. Interestingly, introducing Pt(II) into the copolymer backbone can evidently improve the NLO property or unexpectedly switch the NLO response from saturable absorption to reverse saturable absorption. Meanwhile, both copolymers are successfully employed as optical limiting materials and exhibit broadband optical limiting abilities. Therefore, we present an efficient strategy toward broadband NLO materials, which may significantly facilitate the understanding of organic molecular structure-property relationship and promote their practical application.

Conjugated molecules with low lying LUMO levels are demanding for the development of air stable n-type organic semiconductors. In this paper, we report a new A-D-A'-D-A conjugated molecule (DAPDCV) entailing diazapentalene (DAP) and dicyanovinylene groups as electron accepting units. Both theoretical and electrochemical studies manifest that the incorporation of DAP unit in the conjugated molecule can effectively lower the LUMO energy level. Accordingly, thin film of DAPDCV shows n-type semiconducting behavior with electron mobility up to 0.16 cm2 ⋅V-1 ⋅s-1 after thermal annealing under N2 atmosphere. Moreover, thin film of DAPDCV also shows stable n-type transporting property in air with mobility reaching 0.078 cm2 ⋅V-1 ⋅s-1 .

A highly selective and red emissive fluorescent probe (HCyNB) for penicillin G amidase (PGA) has been prepared in a simple two-step process. After enzymatic reaction, HCyNB showed a fast response to PGA and afforded a light-up red fluorescence assay of PGA with a detection limit of 0.067 U L−1, without interference from other biologically-relevant species and enzymes, including ROS. The easy synthesis, fast response, good sensitivity, remarkable selectivity and pH independence render HCyNB an outstanding tool for bioimaging of endogenous PGA in penicillinase-producing Bacillus subtilis.

A systematic combination strategy is proposed for overcoming cisplatin resistance using near-infrared (NIR)-light-triggered hyperthermia. A new photothermal polymer DAP-F is complexed with a reduction-sensitive amphiphilic polymer P1 to form F-NPs with photothermal effect. Subsequently, to build the final nanosystem F-Pt-NPs, F-NPs are combined with Pt-NPs, which are obtained by encapsulating a Pt(IV) prodrug with P1. Mild hyperthermia (43 °C), generated from F-Pt-NPs induced by an 808 nm NIR laser, have various effects such as: i) enhancing the cellular membrane permeability to promote the uptake of drugs; ii) activating cisplatin by accelerating the glutathione consumption; iii) increasing the Pt-DNA adducts formation and possibly the formation of a portion of irreparable Pt-DNA interstrand crosslinks, thereby inhibiting the repair of DNA. In vitro, it is found that even on cisplatin-resistant A549DDP cells, the IC50 of F-Pt-NPs (43 °C) is only 7.0 × 10-6 m Pt mL-1 . In vivo, on a patient-derived xenograft model of multidrug resistant lung cancer, the efficacy of the F-Pt-NPs (43 °C) treatment group shows a tumor inhibition rate of 94%. Taken together, here, an important perspective of resolving cascade drug resistance with the assistance of mild hyperthermia triggered by NIR light is presented, which can be of great significance for clinic translation.

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.

The diallene-containing compound

Rigid and planar conjugated molecules have substantial significance due to their potential applications in organic electronics. Herein we report two highly fused ladder type conjugated molecules, TTCTTC and TTTCTTTC, with up to 10 fused rings in which the fused-thiophene rings are fused to the chromeno[6,5,4-def]chromene unit. Both molecules show high HOMO levels and accordingly they can be oxidized into their radical cations with absorptions extending to 1300 nm in the presence of trifluoroacetic acid. Thin films of TTCTTC and TTTCTTTC exhibit p-type semiconductor properties with hole mobilities up to 0.39 cm2 V−1 s−1. Moreover, TTCTTC shows a high fluorescence quantum yield of up to 16.5% in the solid state.