Vinylcyclopropanes (VCPs) are commonly used in transition‐metal‐catalyzed cycloadditions, and the utilization of their recently realized reactivities to construct new cyclic architectures is of great ...significance in modern synthetic chemistry. Herein, a palladium‐catalyzed, visible‐light‐driven, asymmetric 5+2 cycloaddition of VCPs with α‐diazoketones is accomplished by switching the reactivity of the Pd‐containing dipolar intermediate from an all‐carbon 1,3‐dipole to an oxo‐1,5‐dipole. Enantioenriched seven‐membered lactones were produced with good reaction efficiencies and selectivities (23 examples, 52–92 % yields with up to 99:1 er and 12.5:1 dr). In addition, computational investigations were performed to rationalize the observed high chemo‐ and periselectivities.
By switching the reactivity of Pd‐containing dipolar intermediates from all‐carbon 1,3‐dipoles to oxo‐1,5‐dipoles, Pd‐catalyzed asymmetric 5+2 cycloadditions of vinylcyclopropanes (VCPs) with photogenerated ketenes are achieved. A variety of chiral seven‐membered lactone‐fused polycyclic molecules are produced with good reaction efficiency and selectivity.
Cuticular waxes are complex mixtures of very-long-chain fatty acids (VLCFAs) and their derivatives, forming a natural barrier on aerial surfaces of terrestrial plants against biotic and abiotic ...stresses. In VLCFA biosynthesis, β-ketoacyl-CoA synthase (KCS) is the key enzyme, catalyzing the first reaction in fatty acid elongation and determining substrate specificity. We isolated a rice (Oryza sativa) wax crystal-sparse leaf 4 (WSL4) gene using a map-based cloning strategy. WSL4 is predicted to encode a KCS, a homolog of Arabidopsis (Arabidopsis thaliana) CER6. Complementation of the mutant wsl4-1 with WSL4 genomic DNA rescued the cuticular wax-deficient phenotype, confirming the function of WSL4. The load of wax components longer than 30 carbons (C30) and C28 were reduced markedly in wsl4-1 and wsl4-2 mutants, respectively. Overexpression of WSL4 increased the cuticular wax load in rice leaves. We further isolated a cofactor of WSL4, OsCER2, a homolog of Arabidopsis CER2, by coimmunoprecipitation and confirmed their physical interaction by split-ubiquitin yeast two-hybrid experiments. Expression of WSL4 alone in elo3 yeast cells resulted in increased C24 but did not produce VLCFAs of greater length, whereas expressing OsCER2 alone showed no effect. Coexpression of WSL4 and OsCER2 in elo3 yeast cells yielded fatty acids up to C30. OsCER2 with a mutated HxxxD motif (H172E, D176A, and D176H) interrupted its interaction with WSL4 and failed to elongate VLCFAs past C24 when expressed with WSL4 in elo3 yeast cells. These results demonstrated that WSL4 was involved in VLCFA elongation beyond C22 and that elongation beyond C24 required the participation of OsCER2.
The endoplasmic reticulum (ER) quality control system monitors protein homeostasis and relies on the activity of many molecular chaperones. Binding immunoglobulin protein (BiP) is a major ER luminal ...chaperone that is involved in most functions of the organelle. BiP activity is tightly regulated by nucleotide exchange factors (NEFs). However, information about NEFs in plants is limited. We obtained a Fes1-like protein (OsFes1C) through isobaric tags for relative and absolute quantitation-based proteomics analysis of ER-stressed rice (Oryza sativa) seeds. Unlike its homologs in yeast and mammals, which are located in the cytosol and respond to heat stress, OsFes1C is an ER membrane protein and responds to ER and salt stresses. OsFes1C interacts directly with OsBiP1 and the interaction is inhibited by ATP but promoted by ADP, suggesting that OsFes1C acts as a potential NEF of OsBiP1 in vivo. Overexpression or suppression of OsFes1C led to hypersensitivity to ER stress and affected the growth of rice. Furthermore, we established that OsFes1C directly interacts with a putative salt response protein and is involved in the salt response. Taken together, our study marks an important step toward elucidating the functional mechanisms of an identified ER stress response factor in rice.
Room temperature phosphorescent (RTP) carbon dots have attracted considerable interest due to their fundamental importance and potential applications in optoelectronic devices, sensing, bioimaging ...and document security. The preparation method of RTP carbon dots is based on the formation of the C&z.dbd;N (or C&z.dbd;O) groups and hydrogen bond. Herein, we have added acrylamide in the reaction system to form hydrogen bonds and stabilize the triplet excitons. Thus, the nontoxic RTP carbon dots (NCDs) were designed and prepared
via
a one-step hydrothermal method. The nitrogen element (N) in the NCDs can effectively increase their fluorescence intensity, while the produced C&z.dbd;N bonds promote the formation of triplet excitons. More importantly, the acrylic amide and the as-generated polyacrylamide (PAM) on the surface of NCDs could easily connect with the as-prepared pyridinic N
via
the reaction between citric acid and urea, and formed the hydrogen bond that could stablilize the triplet excitons. Hence, NCDs exhibit stable phosphorescence properties. We further show the promising application of the as-prepared aqueous NCDs as a new smart concealed and potential security ink.
The room-temperature-phosphorescent carbon dots as a security ink are applied in information encryption and the concealment of complex pattern fields.
Sunitinib resistance is a major challenge for advanced renal cell carcinoma (RCC). Understanding the underlying mechanisms and developing effective strategies against sunitinib resistance are highly ...desired in the clinic. Here we identified an lncRNA, named lncARSR (lncRNA Activated in RCC with Sunitinib Resistance), which correlated with clinically poor sunitinib response. lncARSR promoted sunitinib resistance via competitively binding miR-34/miR-449 to facilitate AXL and c-MET expression in RCC cells. Furthermore, bioactive lncARSR could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating sunitinib resistance. Treatment of sunitinib-resistant RCC with locked nucleic acids targeting lncARSR or an AXL/c-MET inhibitor restored sunitinib response. Therefore, lncARSR may serve as a predictor and a potential therapeutic target for sunitinib resistance.
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•lncARSR promotes sunitinib resistance and predicts poor response of RCC patients•Intercellular transfer of lncARSR by exosomes disseminates sunitinib resistance•lncARSR acts as a ceRNA for miR-34 and miR-449 to promote AXL and c-MET expression•Targeting lncARSR or AXL/c-MET in sunitinib-resistant RCC restores drug sensitivity
Qu et al. identify lncARSR as a mediator of sunitinib resistance in renal cell carcinoma by acting as a competing endogenous RNA for miR-34 and miR-449, thereby increasing expression of their targets AXL and c-MET, and show that exosome-mediated transmission of lncARSR can confer resistance to sensitive cells.
To investigate the effects of short‐term salinity treatment on muscle quality and earthy and musty off‐flavour compounds of freshwater fish, adult grass carp (1.25 ± 0.25 kg) and black carp (1.50 ± ...0.30 kg) were reared at water salinities of 0‰, 5‰ and 7.5‰for 48 h. Muscle nutrients, amino acid, and fatty acid contents, texture properties, and earthy and musty off‐flavour compounds were then determined. The content of total amino acid (TAA), Lys, Arg and essential amino acid index (EAAI) in the muscle of C7.5 group were elevated significantly compared with that in the control group (p < 0.05). The content of delicious amino acids (DAA) and EAAI in the muscle of M7.5 group was significantly higher than M0 and M5 groups (p < 0.05). The fatty acid content of the muscle was affected by salinity. In grass carp, the saturated fatty acid (SFA) content level was decreased significantly in the C5 and C7.5 groups (p < 0.05), while the monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) content levels were increased significantly in the C5 and C7.5 groups (p < 0.05). The ratio of n3/n6 PUFA increased significantly in the C7.5 group (p < 0.05). The PUFA content and the n3/n6 PUFA ratio were increased significantly in the M7.5 group (p < 0.05). With increasing salinity, the relative content levels of volatile compounds causing earthy and musty off‐flavour in muscle were decreased significantly in 5‰ and 7.5‰ salinity groups both grass carp and black carp (p < 0.05). The textural properties of muscle, such as hardness, springiness, gumminess and chewiness, were improved in the C7.5 and M5 groups. These results suggest that a short‐term salinity treatment in freshwater fish prior to selling can effectively improve muscle quality and decrease the content of earthy and musty off‐flavour compounds, with ideal salinities of 5‰ or 7.5‰ for grass carp and 7.5‰ for black carp.
Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell ...death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD
loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD
loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.
Enhanced salt tolerance of rice seedlings by abscisic acid (ABA) pretreatment was observed from phenotypic and physiological analyses. Total proteins from rice roots treated with ABA plus subsequent ...salt stress were analyzed by using proteomics method. Results showed that, 40 protein spots were uniquely upregulated in the seedlings under the condition of ABA pretreatment plus subsequent salt stress, whereas only 16 under the condition of salt treatment. About 78% (31 spots) of the 40 protein spots were only upregulated in the presence of the subsequent salt stress, indicating that plants might have an economical strategy to prevent energy loss under a false alarm. The results also showed that more enzymes involved in energy metabolism, defense, primary metabolism, etc. were upregulated uniquely in ABA-pretreated rice seedlings, suggesting more abundant energy supply, more active anabolism (nitrogen, nucleotide acid, carbohydrate, etc), and more comprehensive defense systems in ABA-pretreated seedlings than in salt stressed ones.
To critically review the currently available evidence of studies comparing robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN).
A comprehensive review of the literature from Pubmed, ...Web of Science and Scopus was performed in October 2013. All relevant studies comparing RPN with OPN were included for further screening. A cumulative meta-analysis of all comparative studies was performed and publication bias was assessed by a funnel plot.
Eight studies were included for the analysis, including a total of 3418 patients (757 patients in the robotic group and 2661 patients in the open group). Although RPN procedures had a longer operative time (weighted mean difference WMD: 40.89; 95% confidence interval CI, 14.39-67.40; p = 0.002), patients in this group benefited from a lower perioperative complication rate (19.3% for RPN and 29.5% for OPN; odds ratio OR: 0.53; 95%CI, 0.42-0.67; p<0.00001), shorter hospital stay (WMD: -2.78; 95%CI, -3.36 to -1.92; p<0.00001), less estimated blood loss(WMD: -106.83; 95%CI, -176.4 to -37.27; p = 0.003). Transfusions, conversion to radical nephrectomy, ischemia time and estimated GFR change, margin status, and overall cost were comparable between the two techniques. The main limitation of the present meta-analysis is the non-randomization of all included studies.
RPN appears to be an efficient alternative to OPN with the advantages of a lower rate of perioperative complications, shorter length of hospital stay and less blood loss. Nevertheless, high quality prospective randomized studies with longer follow-up period are needed to confirm these findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Atherosclerotic plaques belong to the common vascular disease in the aged, which rupture will lead to acute thromboembolic diseases, the leading cause of fatal cardiovascular events. Accumulating ...evidence indicates that the lncRNAs-miRNAs-mRNA regulatory network plays a critical role in atherosclerosis. Based on RNA sequencing (GSE207252), we constructed expression profiles of lncRNAs, microRNAs, and mRNA in the carotid plaque of atherosclerosis patients and analyzed differentially expressed genes (DEGs). We identified three candidate lncRNAs using two algorithms (LASSO and SVM-RFE): lnc_GLRX3, lnc_FGF7-5, and DISC1FP1). LNCipedia, TargetScan, and miRDB databases were used to predict target miRNAs of lncRNAs and target genes of miRNAs. Gene ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA) analysis of DEGs was carried out using the R package clusterProfiler. A PPI network was constructed using the STRING website and visualized by Cytoscape. According to the "MCC" method of the plug-in cytoHubba in Cytoscape, ERCC4 was the top hub gene of the PPI network. We constructed a lncRNA_FGF7-5/lncRNA_GLRX3-miR-2681-5p-ERCC4 regulatory network for carotid plaque using lncRNA-miRNA and miRNA-mRNA pairs. Next, lncRNA_FGF7-5 and lncRNA_GLRX3 targeted miR-2681-5p directly to upregulate ERCC4 expression. Silencing of lncRNA_FGF7-5 and lncRNA_GLRX3 promoted apoptosis and TP53 expression in HUVECs treated with ox-LDL; however, these effects were reversed by ERCC4-overexpression. Taken together, these findings indicated that lncRNA_FGF7-5 and lncRNA_GLRX3 together reduced atherosclerosis-induced apoptosis of HUVECs via targeting miR-2681-5p to increase ERCC4 expression, thereby preventing the formation of carotid plaque and finally inhibiting atherosclerosis progression.
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