The first catalytic asymmetric (4+3) cyclization of in situ generated ortho‐quinone methides with 2‐indolylmethanols has been established, which constructed seven‐membered heterocycles in high yields ...(up to 95 %) and excellent enantioselectivity (up to 98 %). This approach not only represents the first catalytic asymmetric (4+3) cyclization of o‐hydroxybenzyl alcohols, but also enabled an unprecedented catalytic asymmetric (4+3) cyclization of 2‐indolylmethanols. In addition, a scarcely reported catalytic asymmetric (4+3) cyclization of para‐quinone methide derivatives was accomplished.
The first catalytic asymmetric (4+3) cyclization of in situ generated ortho‐quinone methides with 2‐indolylmethanols was developed, and was used to construct seven‐membered heterocycles in high yields and excellent enantioselectivity. This approach represents the first catalytic asymmetric (4+3) cyclization of o‐hydroxybenzyl alcohols, and also enabled the unprecedented catalytic asymmetric (4+3) cyclization of 2‐indolylmethanols.
Efficient and selective dehydrogenation of formic acid is a key challenge for a fuel‐cell‐based hydrogen economy. Though the development of heterogeneous catalysts has received much progress, their ...catalytic activity remains insufficient. Moreover, the design principle of such catalysts are still unclear. Here, experimental and theoretical studies on a series of mono‐/bi‐metallic nanoparticles supported on a NH2‐N‐rGO substrate are combined for formic acid dehydrogenation where the surface energy of a metal is taken as a relevant indicator for the adsorption ability of the catalyst for guiding catalyst design. The AuPd/NH2‐N‐rGO catalyst shows record catalytic activity by reducing the energy barrier of rate controlling steps of formate adsorption and hydrogen desorption. The obtained excellent results both in experiments and simulations could be extended to other important systems, providing a general guideline to design more efficient catalysts.
A AuPd/NH2‐N‐rGO catalyst shows supreme catalytic performance for the decomposition of formic acid at room temperature, with a turnover frequency (TOF) of 4445.6 h−1. Developments in the experiments and simulations of high‐performance catalysts may promote the practical application of formic acid as a promising hydrogen storage material.
Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting step in hepatic gluconeogenesis pathway to maintain blood glucose levels. Mammalian cells express two PCK genes, ...encoding for a cytoplasmic (PCPEK-C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively. Increased expressions of both PCK genes are found in cancer of several organs, including colon, lung, and skin, and linked to increased anabolic metabolism and cell proliferation. Here, we report that the expressions of both PCK1 and PCK2 genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK expression was associated with poor prognosis in patients with HCC. Forced expression of either PCK1 or PCK2 in liver cancer cell lines results in severe apoptosis under the condition of glucose deprivation and suppressed liver tumorigenesis in mice. Mechanistically, we show that the pro-apoptotic effect of PCK1 requires its catalytic activity. We demonstrate that forced PCK1 expression in glucose-starved liver cancer cells induced TCA cataplerosis, leading to energy crisis and oxidative stress. Replenishing TCA intermediate α-ketoglutarate or inhibition of reactive oxygen species production blocked the cell death caused by PCK expression. Taken together, our data reveal that PCK1 is detrimental to malignant hepatocytes and suggest activating PCK1 expression as a potential treatment strategy for patients with HCC.
Background and Purpose
Atherosclerosis induced by cyclosporine A (CsA), an inhibitor of the calcineurin/nuclear factor of activated T cells (NFAT) pathway, is a major concern after organ ...transplantation. However, the atherosclerotic mechanisms of CsA remain obscure. We previously demonstrated that calcineurin/NFAT signalling inhibition contributes to atherogenesis via suppressing microRNA‐204 (miR‐204) transcription. We therefore hypothesised that miR‐204 is involved in the development of CsA‐induced atherosclerosis.
Experimental Approach
ApoE−/− mice with macrophage‐miR‐204 overexpression were generated to determine the effects of miR‐204 on CsA‐induced atherosclerosis. Luciferase reporter assays and chromatin immunoprecipitation sequencing were performed to explore the targets mediating miR‐204 effects.
Key Results
CsA alone did not significantly affect atherosclerotic lesions or serum lipid levels. However, it exacerbated high‐fat diet‐induced atherosclerosis and hyperlipidemia in C57BL/6J and ApoE−/− mice, respectively. miR‐204 levels decreased in circulating monocytes and plaque lesions during CsA‐induced atherosclerosis. The upregulation of miR‐204 in macrophages inhibited CsA‐induced atherosclerotic plaque formation but did not affect serum lipid levels. miR‐204 limited the CsA‐induced foam cell formation by reducing the expression of the scavenger receptors SR‐BII and CD36. SR‐BII was post‐transcriptionally regulated by mature miR‐204‐5p via 3′‐UTR targeting. Additionally, nuclear‐localised miR‐204‐3p prevented the CsA‐induced binding of Ago2 to the CD36 promoter, suppressing CD36 transcription. SR‐BII or CD36 expression restoration dampened the beneficial effects of miR‐204 on CsA‐induced atherosclerosis.
Conclusion and Implications
Macrophage miR‐204 ameliorates CsA‐induced atherosclerosis, suggesting that miR‐204 may be a potential target for the prevention and treatment of CsA‐related atherosclerotic side effects.
Acute renal injury (AKI) causes a long-term risk for progressing into chronic kidney disease (CKD) and interstitial fibrosis. Yes-associated protein (YAP), a key transcriptional cofactor in Hippo ...signaling pathway, shuttles between the cytoplasm and nucleus, which is required for the renal tubular epithelial cells repair in the acute phase of AKI. In this study we investigated the role of YAP during ischemia-reperfusion (IR)-induced AKI to CKD. Mice were subjected to left kidney IR followed by removal of the right kidney on the day before tissue harvests. Mouse shRNA expression adenovirus (Ad-shYAP or Ad-shKLF4) and mouse KLF4 expression adenovirus (Ad-KLF4) were delivered to mice by intrarenal injection on D7 after IR. We showed that the expression and nucleus distribution of YAP were persistently increased until the end of experiment (D21 after IR). The sustained activation of YAP in post-acute phase of AKI was accompanied by renal dysfunction and interstitial fibrosis. Knockdown of YAP significantly attenuated IR-induced renal dysfunction and decreased the expression of fibrogenic factors TGF-β and CTGF in the kidney. We showed that the expression of the transcription factor KLF4, lined on the upstream of YAP, was also persistently increased. Knockdown on KLF4 attenuated YAP increase and nuclear translocation as well as renal functional deterioration and interstitial fibrosis in IR mice, whereas KLF4 overexpression caused opposite effects. KLF4 increased the expression of ITCH, and ITCH facilitated YAP nuclear translocation via degrading LATS1. Furthermore, we demonstrated in primary cultured renal tubular cells that KLF4 bound to the promoter region of YAP and positively regulates YAP expression. In biopsy sample from CKD patients, we also observed increased expression and nuclear distribution of YAP. In conclusion, the activation of YAP in the post-acute phase of AKI is implicated in renal functional deterioration and fibrosis although it exhibits beneficial effect in acute phase. Reprogramming factor KLF4 is responsible for the persistent activation of YAP. Blocking the activation of KLF4-YAP pathway might be a way to prevent the transition of AKI into CKD.
We theoretically and experimentally proposed a new structure of ultra-wideband and thin perfect metamaterial absorber loaded with lumped resistances. The thin absorber was composed of four dielectric ...layers, the metallic double split ring resonators (MDSRR) microstructures and a set of lumped resistors. The mechanism of the ultra-wideband absorption was analyzed and parametric study was also carried out to achieve ultra-wideband operation. The features of ultra-wideband, polarization-insensitivity, and angle-immune absorption were systematically characterized by the angular absorption spectrum, the near electric-field, the surface current distributions and dielectric and ohmic losses. Numerical results show that the proposed metamaterial absorber achieved perfect absorption with absorptivity larger than 80% at the normal incidences within 4.52~25.42 GHz (an absolute bandwidth of 20.9GHz), corresponding to a fractional bandwidth of 139.6%. For verification, a thin metamaterial absorber was implemented using the common printed circuit board method and then measured in a microwave anechoic chamber. Numerical and experimental results agreed well with each other and verified the desired polarization-insensitive ultra-wideband perfect absorption.
Under cooperative catalysis of iridium and a Brønsted acid, different C4-substituted azlactones react with vinyl benzoxazinones via a formal 4+2 cycloaddition or substitution reaction in a chemo- and ...stereoselective mode. Furthermore, the catalytic asymmetric version of the formal 4+2 cycloaddition established cooperative catalysis of iridium and a chiral thiourea-tertiary amine.
In situ forming gel polymer electrolyte (GPE) is one of the most feasible ways to improve the safety and cycle performances of lithium metal batteries with high energy density. However, most of the ...in situ formed GPEs are not compatible with high‐voltage cathode materials. Here, this work provides a novel strategy to in situ form GPE based on the mechanism of Ritter reaction. The Ritter reaction in liquid electrolyte has the advantage of appropriate reaction temperature and no additional additives. The polymer chains are cross‐linked by amide groups with the formation of GPE with superior electrochemical properties. The GPE has high ionic conductivity (1.84 mS cm−1), wide electrochemical stability window (>5.25 V) and high lithium ion transference number (≈0.78), compatible with high‐voltage cathode materials. The Li|LiNi0.6Co0.2Mn0.2O2 batteries with in situ formed GPE show excellent long‐term cycle stability (93.4%, 300 cycles). The density functional theory calculation and X‐ray photoelectron spectroscopy results verify that the amide and nitrile groups are beneficial for stabilizing cathode structure and promoting uniform Li deposition on Li anode. Furthermore, the in situ formed GPE exhibits excellent electrochemical performance in Graphite|LiMn2O4 and Graphite|LiNi0.5Co0.2Mn0.3O2 pouch batteries. This approach is adaptable to current battery technologies, which will be sure to promote the development of high energy‐density lithium‐ion batteries.
Gel polymer electrolyte with high ionic conductivity, wide electrochemical stability window and high lithium‐ion transference number is developed. It can improve the cycle performance of lithium metal batteries by stabilizing cathode structure and promoting uniform Li deposition, which is also applicable to current battery technologies.
A simple and practical method for the synthesis of alkenyl dithiocyanates and alkenyl diselenocyanates has been developed via stereoselective difunctionalization of alkynes with NaSCN or KSeCN at ...room temperature. Through this methodology, a series of alkenyl dithiocyanates and alkenyl diselenocyanates could be efficiently and conveniently obtained in moderate to good yields under mild and metal-free conditions by the simple use of oxone and PhI(OAc)2 as the oxidants.
PDF
