Medium-sized rings, including those embedded in bridged and fused bicyclic scaffolds, are common core structures of myriad bioactive molecules. Among various synthetic strategies towards their ...synthesis, intermolecular higher-order cycloaddition provides great potential to build complex medium-sized rings from simple building blocks. Unfortunately, such transformations are often plagued with competitive reaction pathways and low levels of site- and stereoselectivity. Herein, we report catalyst-controlled divergent access to three classes of medium-sized bicyclic compounds in high efficiency and stereoselectivity, by palladium-catalysed cycloadditions of tropones with γ-methylidene-δ-valerolactones. Mechanistic studies and density functional theory calculations disclosed that the divergent reactions stem from the different reaction profiles of the diastereomeric intermediates. While one undergoes either O- or C-allylation to provide 5.5.0 or 4.4.1 bicyclic compounds, the unique conformation of the other diastereomer allows an unconventional alkene isomerization to deliver bridgehead alkene-containing bicyclo4.4.1 compounds. The conversion of these products to diverse complex polycyclic scaffolds has also been demonstrated.
Bimetallic nanomaterials, which exhibit a combination of the properties associated with two different metals, have enabled innovative applications in nanoscience and nanotechnology. Here, we ...introduce the fabrication of dendritic Au/Ag bimetallic nanostructures for surface-enhanced Raman scattering (SERS) and catalytic applications. The dendritic Au/Ag bimetallic nanostructures were prepared by combining the electrochemical deposition and replacement reaction. The formation of Au nanoparticle shell on the surface of Ag dendrites greatly improves the stability of dendritic nanostructures, followed by a significant SERS enhancement. In addition, these dendritic Au/Ag bimetallic nanostructures are extremely efficient in degrading 4-nitrophenol (4-NP) compared with the initial dendritic Ag nanostructures. These experimental results indicate the great potential of the dendritic Au/Ag bimetallic nanostructures for the development of excellent SERS substrate and highly efficient catalysts.
Acute lung injury (ALI) is a severe health issue with significant morbidity and mortality. Artemisinin is used for the treatment of fever and malaria in clinical practice. Dihydroartemisinin (DHA), ...the major active metabolite of artemisinin, plays a role in anti‑organizational fibrosis and anti‑neuronal cell death. However, whether DHA can attenuate ALI remains unclear. The current study thus examined the effects of DHA on ALI and primary macrophages. The results revealed that DHA attenuated lipopolysaccharide (LPS)‑induced pulmonary pathological damage. DHA suppressed the LPS‑induced infiltration of inflammatory cells, the elevation of myeloperoxidase activity, oxidative stress and the production of pro‑inflammatory cytokines, including interleukin (IL)‑1β, tumor necrosis factor‑α, and IL‑6. Furthermore, DHA reduced the LPS‑induced inflammatory response by suppressing the degradation of I‑κB and the nuclear translocation of nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB)/p65 in vivo and in vitro. DHA activated the nuclear factor‑erythroid 2 related factor 2 (Nrf2) pathway, which was suppressed by LPS treatment. The Nrf2 inhibitor, ML385, diminished the protective effects of DHA against LPS‑induced inflammation in macrophages. On the whole, the findings of this study demonstrate that DHA exerts therapeutic effects against LPS‑induced ALI by inhibiting the Nrf2‑mediated NF‑κB activation in macrophages. The present study also confirmed the therapeutic effects of DHA in mice with LPS‑induced ALI. Thus, these findings demonstrate that DHA exhibits anti‑inflammatory activities and may be a therapeutic candidate for the treatment of ALI.
Studies have shown that the release of endogenous glutamate (Glu) participates in lung injury by activating N-methyl-D-aspartate receptor (NMDAR), but the mechanism is still unclear. This study was ...to investigate the effects and related mechanisms of Glu on the lipid synthesis of pulmonary surfactant (PS) in isolated rat lung tissues.
The cultured lung tissues of adult SD rats were treated with Glu. The amount of 3H-choline incorporation into phosphatidylcholine (PC) was detected. RT-PCR and Western blot were used to detect the changes of mRNA and protein expression of cytidine triphosphate: phosphocholine cytidylyltransferase alpha (CCTα), a key regulatory enzyme in PC biosynthesis. Western blot was used to detect the expression of NMDAR1, which is a functional subunit of NMDAR. Specific protein 1 (Sp1) expression plasmids were used. After transfected with Sp1 expression plasmids, the mRNA and protein levels of CCTα were detected by RT-PCR and Western blot in A549 cells. After treated with NMDA and MK-801, the mRNA and protein levels of Sp1 were detected by RT-PCR and Western blot in A549 cells.
Glu decreased the incorporation of 3H-choline into PC in a concentration- and time- dependent manner. Glu treatment significantly reduced the mRNA and protein levels of CCTα in lungs. Glu treatment up-regulated NMDAR1 protein expression, and the NMDAR blocker MK-801 could partially reverse the reduction of 3H-choline incorporation induced by Glu (10-4 mol/L) in lungs. After transfected with Sp1 plasmid for 30 h, the mRNA and protein expression levels of CCTα were increased and the protein expression of Sp1 was also up-regulated. After A549 cells were treated with NMDA, the level of Sp1 mRNA did not change significantly, but the expression of nucleus protein in Sp1 was significantly decreased, while the expression of cytoplasmic protein was significantly increased. However, MK-801could reverse these changes.
Glu reduced the biosynthesis of the main lipid PC in PS and inhibited CCTα expression by activating NMDAR, which were mediated by the inhibition of the nuclear translocation of Sp1 and the promoter activity of CCTα. In conclusion, NMDAR-mediated Glu toxicity leading to impaired PS synthesis may be a potential pathogenesis of lung injury.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Overactivation of the N-methyl-d-aspartate (NMDA) receptor promotes oxidative stress, aggravates the inflammatory response and induces excitotoxic lung injury. NMDA is a synthetic agonist that ...selectively activates the NMDA receptor. Oleanolic acid (OA) is a natural anti-inflammatory and antioxidant compound. This study investigated the effect and possible mechanism of OA on NMDA-induced acute lung injury (ALI) in mice. OA pretreatment alleviated NMDA-induced histological lung changes and ameliorated pulmonary oedema and pulmonary permeability. At the same time, OA inhibited inflammatory cell infiltration and decreased the levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in the lung and bronchoalveolar lavage fluid (BALF). OA markedly decreased malondialdehyde (MDA) production and increased the superoxide dismutase (SOD) and glutathione (GSH) contents of the lung in vivo. Meanwhile, we first found that NMDA increased LDH activity and decreased cell viability, and induced oxidative stress and apoptosis in mouse lung epithelial (MLE)-12 cells. By employing SRT1720 and sirtinol, the activator and inhibitor of sirtuin 1 (SIRT1), we found that SRT1720 partially eliminated the increase in ROS，and sirtinol further promoted the increase in ROS caused by NMDA. OA increased MLE-12 cells viability and attenuated oxidative stress after NMDA challenge in vitro. OA suppressed NMDA-induced MLE-12 cells apoptosis, while sirtinol inhibited the effect of OA. In addition, OA significantly upregulated the levels of SIRT1, nuclear-related factor 2(Nrf2) and Bcl-2 protein and downregulated the levels of acetylated nuclear factor-kappa B (NF-κB), NLRP3 and Bax protein. In conclusion, OA attenuated NMDA-induced excitotoxic lung injury, potentially through its anti-inflammatory, antioxidative stress and anti-apoptotic effects. The mechanism may be related to activating SIRT1 and reducing NF-κB acetylation.
•NMDA can induce apoptosis of lung epithelial (MLE)-12 cells;•SIRT1 plays a role in NMDA-induced apoptosis of lung epithelial cells;•Oleanolic acid can reduce apoptosis of lung epithelial cells induced by NMDA;•Oleanolic acid can improve excitatory lung injury induced by NMDA;•Oleanolic acid can up-regulate the expression SIRT1 and reduce acetylation of p65.
In order to remarkably enhance the absorption capability of (CH
NH
)PbI
, a tunable narrow-band (CH
NH
)PbI
-based perfect absorber based on the critical coupling with guided resonance is proposed. ...By using the finite-difference time-domain (FDTD) simulations, a complete absorption peak is achieved at the wavelength of 1310 nm. Moreover, we have compared the simulation results with theoretical calculations, which agree well with each other. By changing related structural parameters, the wavelength of absorption peak can be tuned effectively. Furthermore, the proposed absorber can tolerate a relatively wide range of incident angles and demonstrate polarization-independence. In addition to (CH
NH
)PbI
, the complete optical absorption in the other halide perovskites can be realized by the same mechanism.
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival ...is approximately 3–5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant
Asarum heterotropoides
. In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-β1-induced fibroblast-to-myofibroblast transition
in vitro
, while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-β but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target.
A suspended monolayer graphene has only about 2.3% absorption rate in visible and infrared band, which limits its optoelectronic applications. To significantly increase graphene’s absorption ...efficiency, a tunable dual-band and polarization-insensitive coherent perfect absorber (CPA) is proposed in the mid-infrared regime, which contains the silicon array coupled in double-layers graphene waveguide. Based on the FDTD methods, dual-band perfect absorption peaks are achieved in 9611 nm and 9924 nm, respectively. Moreover, due to its center symmetric feature, the proposed absorber also demonstrates polarization-insensitive. Meanwhile, the coherent absorption peaks can be all-optically modulated by altering the relative phase between two reverse incident lights. Furthermore, by manipulating the Fermi energies of two graphene layers, two coherent absorption peaks can move over a wide spectrum range, and our designed CPA can also be changed from dual-band CPA to narrowband CPA. Thus, our results can find some potential applications in the field of developing nanophotonic devices with excellent performance working at the mid-infrared regime.
Bone marrow mesenchymal stem cells (BMSCs) have multi-lineage differentiation potential and play an important role in tissue repair. Studies have shown that BMSCs gather at the injured tissue site ...after granulocyte-colony stimulating factor (G-CSF) administration. In this study, we first investigated whether G-CSF could promote BMSC homing to damaged lung tissue induced by bleomycin (BLM) and then investigated whether SDF-1/CXCR4 chemotaxis might be involved in this process. Next, we further studied the potential inhibitory effect of G-CSF administration in mice with lung fibrosis induced by bleomycin. We examined both the antifibrotic effects of G-CSF in mice with bleomycin-induced pulmonary fibrosis in vivo and its effects on the proliferation, differentiation and chemotactic movement of cells in vitro. Flow cytometry, real-time PCR, transwell and Cell Counting Kit-8 (CCK-8) assays were used in this study. The results showed that both preventative and therapeutic G-CSF administration could significantly inhibit bleomycin-induced pulmonary fibrosis. G-CSF enhanced BMSC migration to lung tissues, but this effect could be alleviated by AMD3100, which blocked the SDF-1/CXCR4 axis. We also found that BMSCs could inhibit fibroblast proliferation and transdifferentiation into myofibroblasts through paracrine actions. In conclusion, G-CSF exerted antifibrotic effects in bleomycin-induced lung fibrosis, in part by promoting BMSC homing to injured lung tissues via SDF-1/CXCR4 chemotaxis.
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