A Co-catalyzed highly regio- and enantioselective reductive coupling of alkynes and aldehydes has been developed under visible light photoredox dual catalysis. A variety of enantioenriched allylic ...alcohols have been obtained by using unsymmetrical internal alkynes and commercially available catalyst, chiral ligand, and reagents. It is noteworthy that this approach has considerable advantages, such as excellent regio- (>95:5 for >40 examples), stereo- (up to >95:5 E/Z), and enantioselectivity (92–99% ee, >35 examples) control, mild reaction conditions, broad substrate scope, and good functional group compatibility, making it a great improvement to enantioselective alkyne–aldehyde reductive coupling reactions.
Abstract
We study the crossover from the Bardeen–Cooper–Shrieffer regime to the Bose–Einstein-condensation regime in an anisotropic trapped quantum gas of ultracold fermionic atoms. Using an ...effective two-dimensional Hamiltonian with renormalized interactions between atoms and dressed molecules, we extend the Gaussian pair fluctuation theory to quasi-two-dimensional systems. The equation of state, pair size and sound velocity as well as the convexity parameters of the Goldstone mode are investigated to show how Fermi superfluidity is affected by reduced dimensionality and Gaussian fluctuations at zero temperature in a wide range of crossover. We compare our results with the recent experiment of
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atomic gases and find good agreements.
Autotaxin (ATX) is considered as an interesting drug target for the therapy of several diseases. The goal of the research was to detect new ATX inhibitors which have novel scaffolds by using virtual ...screening. First, based on two diverse receptor-ligand complexes, 14 pharmacophore models were developed, and the 14 models were verified through a big test database. Those pharmacophore models were utilized to accomplish virtual screening. Next, for the purpose of predicting the probable binding poses of compounds and then carrying out further virtual screening, docking-based virtual screening was performed. Moreover, an excellent 3D QSAR model was established, and 3D QSAR-based virtual screening was applied for predicting the activity values of compounds which got through the above two-round screenings. A correlation coefficient r
, which equals 0.988, was supplied by the 3D QSAR model for the training set, and the correlation coefficient r
equaling 0.808 for the test set means that the developed 3D QSAR model is an excellent model. After the filtering was done by the combinatory virtual screening, which is based on the pharmacophore modelling, docking study, and 3D QSAR modelling, we chose nine potent inhibitors with novel scaffolds finally. Furthermore, two potent compounds have been particularly discussed.
A nickel-catalyzed Kumada coupling of aniline derivatives was developed by selective cleavage of aryl C–N bonds under mild reaction conditions. Without preinstallation of an ortho directing group on ...anilines, the cross-coupling reactions of Boc-protected aromatic amines with aryl Grignard reagents afforded unsymmetric biaryls. Mechanistic studies by DFT calculations revealed that the nickel-mediated C–N bond cleavage is the rate-limiting step.
Genome-wide association studies (GWAS) have identified rs11672691 at 19q13 associated with aggressive prostate cancer (PCa). Here, we independently confirmed the finding in a cohort of 2,738 PCa ...patients and discovered the biological mechanism underlying this association. We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated transcript levels of two biologically plausible candidate genes, PCAT19 and CEACAM21, implicated in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. Remarkably, CRISPR/Cas9-mediated single-nucleotide editing showed the direct effect of rs11672691 on PCAT19 and CEACAM21 expression and PCa cellular aggressive phenotype. Clinical data demonstrated synergistic effects of rs11672691 genotype and PCAT19/CEACAM21 gene expression on PCa prognosis. These results provide a plausible mechanism for rs11672691 associated with aggressive PCa and thus lay the ground work for translating this finding to the clinic.
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•SNP rs11672691 at 19q13 associates with aggressive PCa, PCAT19, and CEACAM21 expression•rs11672691 G empowers prognostic factor HOXA2 to elevate its eQTL gene expression•rs11672691 directly impacts gene regulation, PCa cellular phenotype, and progression•rs11672691 genotype and PCAT19 or CEACAM21 expression synergize in PCa prognosis
A non-coding risk allele associated with aggressive prostate cancer creates a transcription factor binding site that in turn promotes oncogenesis by impacting expression of nearby genes.
Both Ganoderma lucidum (GL) and G. sinense (GS) are used as Lingzhi in China. Their functions are assumed to mainly derive from triterpenes and polysaccharides; however, the two species have very ...different triterpenes profiles, if this was the case, then the bioactivity of these two species should differ. Instead, could the polysaccharides be similar, contributing to the shared therapeutic basis? In this study, two main polysaccharide fractions from different batches of GL and GS were systematically compared by a series of chemical and biological experiments. The results showed that the polysaccharides from two species shared the same structural features in terms of mono-/oligo-saccharide profiles, molecular size, sugar linkages, and IR/NMR spectra. In addition, these polysaccharides showed similar tumor-suppressive activity in mice. Further study on RAW264.7 cells indicated that these polysaccharides exhibited similar inducing effects to macrophages, as evaluated in the phagocytosis function, NO/cytokines production, inhibition against the viability and migration of cancer cells. Mechanistic investigation revealed the identical activation via TLR-4 related MAPK/NF-κB signaling pathway and gut-microbiota modulatory effects. In summary, GL and GS polysaccharides presented similar chemical features, antitumor/immunomodulating activities and mechanism; this establishes polysaccharides as the active principles and supports the official use of both species as Lingzhi.
Cancer‐derived exosomes are involved in the development of cancer cachexia. Carnosol, which exhibited ameliorating effects on cancer cachexia of C26 tumour‐bearing mice in our previous study, ...alleviated atrophy of C2C12 myotubes induced by exosomes of C26 tumour cells in the present study. MiR‐183‐5p was found to be rich in C26 cells and C26 exosomes, and miR‐183‐5p mimic could directly induce atrophy of C2C12 myotubes. Carnosol at 5 to 20 μM could dose‐dependently ameliorate the myotube atrophy induced by miR‐183‐5p. Four and a half LIM domain protein 1 (FHL1) was shown to be the direct target of miR‐183‐5p. Increase in myostatin, p‐Smad3, MuRF‐1, Atrogin‐1, HIF‐1α and p‐STAT3 and decrease in mitochondrial respiration were also induced by miR‐183‐5p mimic in C2C12 myotubes. Carnosol could not affect the decrease in FHL‐1 and the activation of STAT3 pathway but could significantly alleviate the increase in myostatin, p‐Smad3, MuRF‐1, Atrogin‐1 and the decrease in mitochondrial respiration induced by miR‐183‐5p. The protective effects of carnosol on myotubes against atrophy of C2C12 myotubes induced by miR‐183‐5p, based on both its inhibiting effects on MuRF‐1 and Atrogin‐1‐mediated protein degradation and its ability of keeping the mitochondrial respiration, might contribute to its ameliorating effects on cancer cachexia.
Functional characterization of disease-causing variants at risk loci has been a significant challenge. Here we report a high-throughput single-nucleotide polymorphisms sequencing (SNPs-seq) ...technology to simultaneously screen hundreds to thousands of SNPs for their allele-dependent protein-binding differences. This technology takes advantage of higher retention rate of protein-bound DNA oligos in protein purification column to quantitatively sequence these SNP-containing oligos. We apply this technology to test prostate cancer-risk loci and observe differential allelic protein binding in a significant number of selected SNPs. We also test a unique application of self-transcribing active regulatory region sequencing (STARR-seq) in characterizing allele-dependent transcriptional regulation and provide detailed functional analysis at two risk loci (RGS17 and ASCL2). Together, we introduce a powerful high-throughput pipeline for large-scale screening of functional SNPs at disease risk loci.
A Pd-catalyzed enantioselective C–H carbonylation by desymmetrization was developed with commercially available L-pyroglutamic acid as chiral ligand. Isoquinolinones were successfully obtained with ...good yields and high enantioselectivities. Mechanistic studies and DFT calculations provided a reasonable reaction pathway.
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