We examine the liquidity of 456 different cryptocurrencies, and show that return predictability diminishes in cryptocurrencies with high market liquidity. We show that whilst Bitcoin returns are ...showing signs of efficiency, numerous cryptocurrencies still exhibit signs of autocorrelation and non-independence. Our findings also show a strong relationship between the Hurst exponent and liquidity on a cross-sectional basis. Therefore, we conclude that liquidity plays a significant role in market efficiency and return predictability of new cryptocurrencies.
•We examine 456 cryptocurrencies.•Return predictability diminishes as liquidity increases in cryptocurrencies.•Volatility decreases as liquidity increases in cryptocurrencies.•There are no signs of an illiquidity premium.
By virtue of a fundamentally new reaction model of azomethine ylide serving as a two‐atom synthon, we present the first example of stereodivergent preparation of γ‐butyrolactones via synergistic ...Cu/Ir‐catalyzed asymmetric cascade allylation/lactonization, and all four stereoisomers of γ‐butyrolactones bearing two vicinal stereocenters are accessible with excellent diastereoselective and enantioselective control. The chiral IrIII‐π‐allyl intermediate was separated and characterized to understand the origin of the regio‐ and stereoselectivity of the initial C−C bond formation process. Control experiments shed some light on the catalyst/substrate and catalyst/catalyst interactions in this dual catalytic system to rationalize the related kinetic/dynamic kinetic resolution process with different catalyst combinations. The enantioenriched γ‐butyrolactone products were converted into an array of structurally complex chiral molecules and organocatalysts that were otherwise inaccessible.
An unprecedented asymmetric cascade allylation/lactonization between racemic aldimine esters and racemic vinylethylene carbonate catalyzed by synergistic Cu/Ir catalysis is presented. The metalated azomethine ylide acts as a two‐atom unit and opens up access to a broad range of γ‐butyrolactones bearing two vicinal stereogenic centers in a stereodivergent manner.
Linear copolymer hosts bearing a number of pillar5arene dangling side chains are synthesized for the facile construction of highly emissive supramolecular polymer networks (SPNs) upon noncovalently ...cross‐linking with a series of tetraphenyethylene (TPE)‐based tetratopic guests terminated with different functional groups through supramolecular host–guest interactions. An extremely high fluorescence quantum yield (98.22%) of the SPNs materials is obtained in tetrahydrofuran (THF) by fine‐tuning the parameters, and meanwhile supramolecular light‐harvesting systems based on spherical supramolecular nanoparticles are constructed by interweaving 9,10‐distyrylanthracene (DSA) and TPE‐based guest molecules of aggregation‐induced emission (AIE) with the copolymer hosts in the mixed solvent of THF/H2O. The present study not only illustrates the restriction of the intramolecular rotations (RIR)‐ruled emission enhancement mechanism regulated particularly by macrocyclic arene‐containing copolymer hosts, but also suggests a new self‐assembly approach to construct high‐performance light‐harvesting materials.
Supramolecular polymer networks and supramolecular nanoparticles based on copolymer hosts bearing a number of pillar5arene dangling side chains and tetraphenyethylene‐based tetratopic guests are fabricated, incorporating high fluorescence quantum yield, tunable emission wavelength, and stable microstructures. This facile strategy suggests a new self‐assembly approach to construct high‐performance light‐harvesting materials.
Conspectus Optically active nitrogen-containing compounds have attracted substantial attention due to their ubiquity in the cores of natural products and bioactive molecules. Among the various ...synthetic approaches to nitrogenous frameworks, catalytic asymmetric 1,3-dipolar cycloadditions are one of the most attractive methods because of their powerful ability to rapidly construct various chiral N-heterocycles. In particular, N-metallated azomethine ylides, common and readily available 1,3-dipoles, have been extensively applied in dipolar cycloaddition reactions. Despite the fact that asymmetric transformations of azomethine ylides have been investigated for decades, most of the efforts have been directed toward the preparation of pyrrolidines using glycinate-derived α-unsubstituted aldimine esters as the precursors of the azomethine ylides. While α-substituted azomethine ylides derived from amino esters other than glycinate have seldom been harnessed, the construction of non-five-membered chiral N-heterocycles via 1,3-dipolar cycloadditions remains underexplored. In addition, the asymmetric α-functionalization of aldimine esters to prepare acyclic nitrogenous compounds such as α-amino acids, in which an in situ-generated N-metallated azomethine ylide serves as the nucleophile, has not been sufficiently described. In this Account, we mainly discuss the achievements we have made in the past decade toward broadening the applications of N-metallated azomethine ylides for the preparation of nitrogen-containing compounds. We began our investigation with the design and synthesis of a new type of chiral ligand, TF-BiphamPhos, which not only coordinates with Lewis acids to activate dipolar species but also serves as an H-bond donor to increase the reactivity of dipolarophiles with significantly enhanced stereochemical control. Using the Cu(I) or Ag(I)/TF-BiphamPhos complex as the catalyst, we achieved highly stereoselective (3+2) cycloadditions of glycinate and non-glycinate-derived azomethine ylides with diverse dipolarophiles, producing a variety of enantioenriched pyrrolidines with multiple stereocenters in a single step. To further expand the synthetic utility of N-metallated azomethine ylides, we successfully developed higher order cycloadditions with fulvenes, tropone, 2-acyl cycloheptatrienes, and pyrazolidinium ylides serving as the reaction partner, and this reaction provides straightforward access to enantioenriched fused piperidines, bridged azabicyclic frameworks, and triazines via (3+6)- and (3+3)-type cycloadditions. Using N-metallated azomethine ylides as the nucleophile, we realized Cu(I)-catalyzed asymmetric 1,4-Michael additions with α,β-unsaturated bisphosphates/Morita–Baylis–Hillman products, furnishing an array of structurally diverse unnatural α-amino acids. Based on the strategy of synergistic activation, we achieved highly efficient dual Cu/Pd and Cu/Ir catalysis for the α-functionalization of aldimine esters via the asymmetric allylic/allenylic alkylation of N-metallated azomethine ylides. Notably, Cu/Ir catalysis allowed the stereodivergent synthesis of α,α-disubstituted α-amino acids via a branched allylic alkylation reaction, in which the two distinct chiral metal catalysts independently have full stereochemical control over the corresponding nucleophile and electrophile. Furthermore, an expedient and stereodivergent preparation of biologically important tetrahydro-γ-carbolines was realized through a Cu/Ir-catalyzed cascade allylation/iso-Pictet–Spengler cyclization. In addition, when the steric congestion in the allylation intermediates was increased, the combined Cu/Ir catalysts provided an asymmetric cascade allylation/2-aza-Cope rearrangement, producing various optically active homoallylic amines with impressive results.
The blood-spinal cord barrier (BSCB), a physical barrier between the blood and spinal cord parenchyma, prevents the toxins, blood cells, and pathogens from entering the spinal cord and maintains a ...tightly controlled chemical balance in the spinal environment, which is necessary for proper neural function. A BSCB disruption, however, plays an important role in primary and secondary injury processes related to spinal cord injury (SCI). After SCI, the structure of the BSCB is broken down, which leads directly to leakage of blood components. At the same time, the permeability of the BSCB is also increased. Repairing the disruption of the BSCB could alleviate the SCI pathology. We review the morphology and pathology of the BSCB and progression of therapeutic methods targeting BSCB in SCI.
Osteoarthritis (OA) is one of the most common diseases leading to physical disability, with age being the main risk factor, and degeneration of articular cartilage is the main focus for the ...pathogenesis of OA. Autophagy is a crucial intracellular homeostasis system recycling flawed macromolecules and cellular organelles to sustain the metabolism of cells. Growing evidences have revealed that autophagy is chondroprotective by regulating apoptosis and repairing the function of damaged chondrocytes. Then, OA is related to autophagy depending on different stages and models. In this review, we discuss the character of autophagy in OA and the process of the autophagy pathway, which can be modulated by some drugs, key molecules and non-coding RNAs (microRNAs, long non-coding RNAs and circular RNAs). More in-depth investigations of autophagy are needed to find therapeutic targets or diagnostic biomarkers through in vitro and in vivo situations, making autophagy a more effective way for OA treatment in the future. The aim of this review is to introduce the concept of autophagy and make readers realize its impact on OA. The database we searched in is PubMed and we used the keywords listed below to find appropriate article resources.
Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular ...carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells(HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.
An unprecedented hydroalkylation of racemic allylic alcohols and racemic ketimine esters enabled by Cu/Ru relay catalysis has been developed via merging the ruthenium‐catalyzed asymmetric ...borrowing‐hydrogen reaction with a copper‐catalyzed asymmetric Michael addition in a one‐pot procedure. The current method enables the efficient preparation of highly functionalized δ‐hydroxyesters bearing 1,4‐nonadjacent stereocenters in good yields with high levels of diastereoselectivity and excellent enantioselectivity under mild reaction conditions. The full complement of the four stereoisomers of hydroalkylation products could be readily accessed by orthogonal permutations of two chiral metal catalysts. The current work highlights the power of relay catalysis for the stereodivergent construction of 1,4‐nonadjacent stereocenters that were otherwise inaccessible.
An unprecedented stereodivergent hydroalkylation of racemic allylic alcohols and racemic ketimine esters enabled by dual Cu/Ru relay catalysis has been developed. Merging the ruthenium‐catalyzed asymmetric borrowing‐hydrogen reaction with a copper‐catalyzed asymmetric Michael addition into a one‐pot procedure provided a route to highly functionalized δ‐hydroxyesters bearing 1,4‐nonadjacent stereocenters in good yields with excellent stereoselectivity under mild reaction conditions.
To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L ...(CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.
Lung adenocarcinoma (ADC) is the predominant histological type of lung cancer, and radiotherapy is one of the current therapeutic strategies for lung cancer treatment. Unfortunately, biological ...complexity and cancer heterogeneity contribute to radioresistance development. Karyopherin α2 (KPNA2) is a member of the importin α family that mediates the nucleocytoplasmic transport of cargo proteins. KPNA2 overexpression is observed across cancer tissues of diverse origins. However, the role of KPNA2 in lung cancer radioresistance is unclear. Herein, we demonstrated that high expression of KPNA2 is positively correlated with radioresistance and cancer stem cell (CSC) properties in lung ADC cells. Radioresistant cells exhibited nuclear accumulation of KPNA2 and its cargos (OCT4 and c‐MYC). Additionally, KPNA2 knockdown regulated CSC‐related gene expression in radioresistant cells. Next‐generation sequencing and bioinformatic analysis revealed that STAT1 activation and nuclear phospholipid scramblase 1 (PLSCR1) are involved in KPNA2‐mediated radioresistance. Endogenous PLSCR1 interacting with KPNA2 and PLSCR1 knockdown suppressed the radioresistance induced by KPNA2 expression. Both STAT1 and PLSCR1 were found to be positively correlated with dysregulated KPNA2 in radioresistant cells and ADC tissues. We further demonstrated a potential positive feedback loop between PLSCR1 and STAT1 in radioresistant cells, and this PLSCR1‐STAT1 loop modulates CSC characteristics. In addition, AKT1 knockdown attenuated the nuclear accumulation of KPNA2 in radioresistant lung cancer cells. Our results collectively support a mechanistic understanding of a novel role for KPNA2 in promoting radioresistance in lung ADC cells.
Nuclear KPNA2 promotes radioresistance and regulates cancer stem cell properties in lung adenocarcinoma cells. A loop between PLSCR1 and STAT1 is involved in KPNA2‐mediated radioresistance.
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