Transition-metal-catalyzed cross-coupling reactions have been well-established as indispensable tools in modern organic synthesis. One of the major research goals in cross-coupling area is expanding ...the scope of the coupling partners. In the past decade, diazo compounds (or their precursors N-tosylhydrazones) have emerged as nucleophilic cross-coupling partners in C–C single bond or CC double bond formations in transition-metal-catalyzed reactions. This type of coupling reaction involves the following general steps. First, the organometallic species is generated by various processes, including oxidative addition, transmetalation, cyclization, C–C bond cleavage, and C–H bond activation. Subsequently, the organometallic species reacts with the diazo substrate to generate metal carbene intermediate, which undergoes rapid migratory insertion to form a C–C bond. The new organometallic species generated from migratory insertion may undergo various transformations. This type of carbene-based coupling has proven to be general: various transition metals including Pd, Cu, Rh, Ni, Co, and Ir are effective catalysts; the scope of the reaction has also been extended to substrates other than diazo compounds; and various cascade processes have also been devised based on the carbene migratory insertion. This review will summarize the achievements made in this field since 2001.
Smartphones are becoming increasingly indispensable in everyday life for most undergraduates in China, and this has been associated with problematic use or addiction. The aim of the current study was ...to investigate the prevalence of smartphone addiction and the associated factors in male and female undergraduates.
This cross-sectional study was conducted in 2016 and included 1441 undergraduate students at Wannan Medical College, China. The Smartphone Addiction Scale short version (SAS-SV) was used to assess smartphone addiction among the students, using accepted cut-offs. Participants' demographic, smartphone usage, and psycho-behavioral data were collected. Multivariate logistic regression models were used to seek associations between smartphone addiction and independent variables among the males and females, separately.
The prevalence of smartphone addiction among participants was 29.8% (30.3% in males and 29.3% in females). Factors associated with smartphone addiction in male students were use of game apps, anxiety, and poor sleep quality. Significant factors for female undergraduates were use of multimedia applications, use of social networking services, depression, anxiety, and poor sleep quality.
Smartphone addiction was common among the medical college students investigated. This study identified associations between smartphone usage, psycho-behavioral factors, and smartphone addiction, and the associations differed between males and females. These results suggest the need for interventions to reduce smartphone addiction among undergraduate students.
The global pandemic of coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable neutralization assay is very important for the development of vaccines and novel ...drugs. In this study, a G protein-deficient vesicular stomatitis virus (VSVdG) bearing a truncated spike protein (S with C-terminal 18 amino acid truncation) was compared to that bearing the full-length spike protein of SARS-CoV-2 and showed much higher efficiency. A neutralization assay was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and hACE2-overexpressing BHK21 cells (BHK21-hACE2 cells). The experimental results can be obtained by automatically counting the number of EGFP-positive cells at 12 h after infection, making the assay convenient and high-throughput. The serum neutralizing titer measured by the VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with that measured by the wild type SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 S protein were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.
In the chemical industry, molecules of interest are based primarily on carbon skeletons. When synthesizing such molecules, the activation of carbon-carbon single bonds (C-C bonds) in simple ...substrates is strategically important: it offers a way of disconnecting such inert bonds, forming more active linkages (for example, between carbon and a transition metal) and eventually producing more versatile scaffolds. The challenge in achieving such activation is the kinetic inertness of C-C bonds and the relative weakness of newly formed carbon-metal bonds. The most common tactic starts with a three- or four-membered carbon-ring system, in which strain release provides a crucial thermodynamic driving force. However, broadly useful methods that are based on catalytic activation of unstrained C-C bonds have proven elusive, because the cleavage process is much less energetically favourable. Here we report a general approach to the catalytic activation of C-C bonds in simple cyclopentanones and some cyclohexanones. The key to our success is the combination of a rhodium pre-catalyst, an N-heterocyclic carbene ligand and an amino-pyridine co-catalyst. When an aryl group is present in the C3 position of cyclopentanone, the less strained C-C bond can be activated; this is followed by activation of a carbon-hydrogen bond in the aryl group, leading to efficient synthesis of functionalized α-tetralones-a common structural motif and versatile building block in organic synthesis. Furthermore, this method can substantially enhance the efficiency of the enantioselective synthesis of some natural products of terpenoids. Density functional theory calculations reveal a mechanism involving an intriguing rhodium-bridged bicyclic intermediate.
Carbon–carbon (C–C) bonds make up the skeletons of most organic molecules. The selective manipulation of C–C bonds offers a direct approach to editing molecular scaffolds but remains challenging. The ...kinetic inertness of C–C bonds can be overcome with transition-metal catalysis, which, nevertheless, relies on a substrate being highly strained or bearing a permanent directing group (DG). The driving force for C–C activation in these cases is strain relief and the formation of a stable metallocycle, respectively. Over the past two decades, a strategy has emerged that uses temporary or removable DGs to effect C–C activation of more common and less strained compounds. A variety of C–C bonds in less strained organic molecules are converted into more reactive transition-metal–carbon (M–C) bonds, enabling downstream transformations as part of diverse synthetic methods. This Review highlights catalytic approaches using temporary or removable DGs to help activate unstrained C–C bonds. The content is organized according to the temporary or removable nature of the DGs and includes applications in the synthesis of natural products or bioactive molecules.Selective manipulation of carbon–carbon bonds provides a direct approach to editing organic scaffolds. This Review describes the catalytic activation of unstrained carbon–carbon bonds enabled by temporary or removable directing groups.
A novel RuII-catalyzed tandem C–H bond activation tool has been successfully developed involving allylation and oxidative cyclization of 2-phenyl indoles with allyl carbonates. This one-pot reaction ...is a new way to synthesize indolo2,1-aisoquinoline units via a simple and efficient process.
Deregulation of the phosphoinositide 3-kinase (PI3K) pathway contributes to the development and progression of tumors. Here, we determine that somatic mutations in PIK3CA (44%), PIK3R1 (17%), AKT3 ...(15%), and PTEN (12%) are prevalent and diverse in Chinese breast cancer patients, with 60 novel mutations identified. A high proportion of tumors harbors multiple mutations, especially PIK3CA plus PIK3R1 mutations (9.0%). Next, we develop a recombination-based mutation barcoding (ReMB) library for impactful mutations conferring clonal advantage in proliferation and drug responses. The highest-ranking PIK3CA and PIK3R1 mutations include previously reported deleterious mutations, as well as mutations with unknown significance. These PIK3CA and PIK3R1 impactful mutations exhibit a mutually exclusive pattern, leading to oncogenesis and hyperactivity of PI3K pathway. The PIK3CA impactful mutations are tightly associated with hormone receptor positivity. Collectively, these findings advance our understanding of PI3K impactful mutations in breast cancer and have important implications for PI3K-targeted therapy in precision oncology.
Abstract
Pro-inflammatory M1 macrophages, via activating hepatic stellate cells, contribute to liver fibrosis. In this study, we examined the mechanism and the significance of a signaling axis, ...METTL3/MALAT1/PTBP1/USP8/TAK1, in regulating pyroptosis and M1 polarization of hepatic macrophages. Liver fibrosis model was established in vivo by CCl
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treatment; M1 polarization was induced in vitro by treating macrophages with lipopolysaccharide or interferon γ. Expressions of METTL3, MALAT1, PTBP1, USP8, and TAK1 were measured by RT-PCR and/or Western blot in Kupffer cells (KCs) isolated from in vivo model or in vitro activated macrophages. Macrophage phenotypes including inflammation (RT-qPCR analysis of a panel of proinflammatory cytokines and ELISA on productions of interleukin (IL)−1β and IL-18) and pyroptosis (Western blot of NLRP3, Caspase-1, and GSDMD) were investigated. The impact of METTL3 on m
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A methylation of MALAT1 was examined by methylated RNA immunoprecipitation (RIP), the interaction between PTBP1 and MALAT1 or USP8 mRNA by combining RNA pull-down, RIP, and RNA stability assays, and the crosstalk between USP8 and TAK1 by co-immunoprecipitation and protein degradation assays. Functional significance of individual component of METTL3/MALAT1/PTBP1/USP8/TAK1 axis was assessed by combining gain-of-function and loss-of-function approaches. In KCs isolated from in vivo liver fibrosis model or in vitro M1-polarized macrophages, METTL3 was up-regulated, and sequentially, it increased MALAT1 level via m
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A methylation, which promoted USP8 mRNA degradation through the interaction with PTBP1. Reduced USP8 expression regulated the ubiquitination and protein stability of TAK1, which promoted pyroptosis and inflammation of macrophages. The signaling cascade METTL3/MALAT1/PTBP1/USP8/TAK1, by essentially stimulating pyroptosis and inflammation of macrophages, aggravates liver fibrosis. Therefore, targeting individual components of this axis may benefit the treatment of liver fibrosis.
Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the 2 main autoimmune thyroid diseases that have both similarities and differences. Determining the genetic basis that distinguishes HT from ...GD is key for a better understanding of the differences between these closely related diseases.
To identify the susceptibility genes for HT in the Chinese cohort and compare susceptibility genes between GD and HT.
In the current study, 18 SNPs from 18 established GD risk loci were selected and then genotyped in 2682 patients with HT, 4980 patients with GD, and 3892 controls. The association analysis between HT and controls and heterogeneity analysis between HT and GD were performed on SPSS, with the logistic regression analysis adjusted for sex and age.
We identified 11 susceptibility loci for HT in the Chinese Han population, with 4 loci, including the rs1265883 in SLAMF6 locus, rs1024161 in CTLA4, rs1521 in HLA-B, and rs5912838 in GPR174/ ITM2A at X chromosome, reaching genome-wide significance of 5 × 10-8. Five loci were reported to be associated with HT for the first time. We also identified 6 susceptibility loci with heterogeneity between GD and HT. Out of them, 4 loci were associated with GD but not with HT, including HLA-DPB1, CD40, TSHR, and TG; the association of HLA-B with GD was stronger than that with HT, but the association of SLAMF6 was reversed.
Our findings suggested that the pathogenesis of HT and GD was different.
Graphene-based nanomaterials, such as graphene oxide (GO) and reduced graphene oxide (rGO), have shown great potentials in drug delivery and photodynamic/photothermal therapy due to their featured ...structure and physicochemical properties. In recent years, their antibacterial potentials have also been exploited. The commonly recognized antibacterial mechanisms include sharp edge-mediated cutting effect, oxidative stress and cell entrapment. This antibacterial activity is very important for human health. As we know, infection with the pathogenic bacteria, especially the drug-resistant ones, is a great threat to human lives. Thus, the development of the antibiotics-independent and drug-free antibacterial agents is of great importance and significance. Graphene-based nanomaterials are a kind of such antibacterial agents. An insight into their properties and antibacterial mechanisms is necessary before they are developed into real products. Herein, we provide a comprehensive understanding of the antibacterial application of graphene-based nanomaterials via summarizing their antibacterial activities against some typical microbial species and discussing their unique mechanisms. In addition, the side-effects and problems in using these nanomaterials are also discussed.
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