Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel β-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated ...with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection.
Methods
In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2.
Results
To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively.
Conclusions
Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.
A peptide-based magnetic chemiluminescence enzyme immunoassay for the detection of SARS-CoV-2 antibodies was developed; 71.4% (197 of 276) and 57.2% (158 of 276) of the COVID-19 inpatients were positive for IgG and IgM against SARS-CoV-2.
Emerging evidence suggests that epithelial‐mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is ...crucial for improving treatment of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC; however, the mechanisms by which miRNAs target the EMT and their therapeutic potential remains largely unknown. To better explore the roles of miRNAs in the EMT process, we established an EMT model in HCC cells by transforming growth factor beta 1 treatment and found that several tumor‐related miRNAs were significantly decreased. Among these miRNAs, miR‐125b expression was most strongly suppressed. We also found down‐regulation of miR‐125b in most HCC cells and clinical specimens, which correlated with cellular differentiation in HCC patients. We then demonstrated that miR‐125b overexpression attenuated EMT phenotype in HCC cancer cells, whereas knockdown of miR‐125b promoted the EMT phenotype in vitro and in vivo. Moreover, we found that miR‐125b attenuated EMT‐associated traits, including chemoresistance, migration, and stemness in HCC cells, and negatively correlated with EMT and cancer stem cell (CSC) marker expressions in HCC specimens. miR‐125b overexpression could inhibit CSC generation and decrease tumor incidence in the mouse xenograft model. Mechanistically, our data revealed that miR‐125b suppressed EMT and EMT‐associated traits of HCC cells by targeting small mothers against decapentaplegic (SMAD)2 and 4. Most important, the therapeutic delivery of synthetic miR‐125b mimics decreased the target molecule of CSC and inhibited metastasis in the mice model. These findings suggest a potential therapeutic treatment of miR‐125b for liver cancer. Conclusion: miR‐125b exerts inhibitory effects on EMT and EMT‐associated traits in HCC by SMAD2 and 4. Ectopic expression of miR‐125b provides a promising strategy to treat HCC. (Hepatology 2015;62:801–815)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Accumulating evidence suggests that Ras GTPase‐activating protein SH3 domain‐binding protein 1 (G3BP1) is very crucial to regulate tumorigenesis and metastasis. Recently, many research works have ...suggested that G3BP1 is overexpressed in many human cancers including esophageal cancer. Nevertheless, the functional roles of G3BP1 in esophageal cancer are still unknown. Here, the results suggested that silencing of G3BP1 inhibited proliferation, migration, and invasion of esophageal cancer cells, whereas overexpression of G3BP1 led to opposite effects on the growth and metastasis. Surprisingly, G3BP1‐depletion had no effect on cell death but caused the arrest of cell cycle in the G0/G1 phase and increased the levels of p53 and p21. In addition, loss of G3BP1 led to a significant elevation of E‐cadherin and decrease of N‐cadherin, Vimentin, Snail, MMP‐9, and MMP‐2. Mechanistically, loss of G3BP1 dramatically suppressed Wnt‐stimulated T‐cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor activity and downregulated its target genes including c‐Myc, Axin2, and cyclin D1. Moreover, knockdown of G3BP1 downregulated the expression levels of p‐PI3K, p‐AKT, and p‐GSK‐3β, but the total PI3K, AKT, and GSK‐3β were not changed. Furthermore, our data proved that the promoting effects of G3BP1‐overexpression on cell proliferation, migration, and invasion could be rescued by PI3K inhibitor LY294002 treatment. Collectively, our results here elucidate that G3BP1‐depletion suppresses proliferation, migration, and invasion capabilities of esophageal cancer cells via the inactivation of Wnt/β‐catenin and PI3K/AKT signaling pathways. Furthermore, our findings imply that G3BP1 can participate in the regulation of esophageal cancer progression, and will be taken as a promising target to treat esophageal cancer.
In our study, we investigated the effects of GTPase‐activating protein SH3 domain‐binding protein 1‐depletion (G3BP1) on cell proliferation, cell cycle, cell death, migration, and invasion of esophageal cancer cells. Our results demonstrated that knockdown of G3BP1 gave rise to inhibition of esophageal cancer cell proliferation, migration, invasion, epithelial‐mesenchymal transition, and cell cycle arrest in the G0/G1 phase through suppressing Wnt/β‐catenin and PI3K/AKT signaling pathways, whereas overexpression of G3BP1 led to opposite the effects on proliferation, migration, and invasion. Our data suggest that G3BP1 plays a crucial role in esophageal cancer progression, and may be a novel prognostic marker and potential therapeutic target for esophageal cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Photoredox-mediated umpolung strategy provides an alternative pattern for functionalization of carbonyl compounds. However, general approaches towards carboxylation of carbonyl compounds ...with CO
2
remain scarce. Herein, we report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of diverse carbonyl compounds with CO
2
by using Lewis acidic chlorosilanes as activating/protecting groups. This strategy is general and practical to generate valuable α-hydroxycarboxylic acids. It works well for challenging alkyl aryl ketones and aryl aldehydes, as well as for α-ketoamides and α-ketoesters, the latter two of which have never been successfully applied in umpolung carboxylations with CO
2
(to the best of our knowledge). This reaction features high selectivity, broad substrate scope, good functional group tolerance, mild reaction conditions and facile derivations of products to bioactive compounds, including oxypheonium, mepenzolate bromide, benactyzine, and tiotropium. Moreover, the formation of carbon radicals and carbanions as well as the key role of chlorosilanes are supported by control experiments.
Inexpensive, safe, and efficient conversion of solar energy to hydrogen from water splitting requires the development of effective and durable photocatalysts. Cu
2
ZnSnS
4
(CZTS), the emerging ...quaternary chalcogenide material for solar energy conversion, possesses many advantages, such as narrow direct band gap (1.5 eV), non-toxic, earth-abundance, and low melting point. Currently, CZTS-based photocatalysts have been extensively investigated for their application as an active photocatalyst in hydrogen evolution from water splitting, while the performance is still highly needed to be improved for the practical applications. In this review, first, the crystal and band structure properties of CZTS are briefly introduced, and afterward, the basic principle of photocatalytic hydrogen evolution from water splitting is discussed. Subsequently, the performance and status of bare CZTS, the combination of CZTS and co-catalysts, and CZTS-based heterojunction photocatalysts for hydrogen evolution are reviewed and discussed in detail. Finally, the issues and challenges currently encountered in the application of CZTS and their possible solutions for developing advanced CZTS photocatalysts are provided.
Graphical abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Natural products possessing unique scaffolds may have antiviral activity but their complex structures hinder facile synthesis. A pharmacophore‐oriented semisynthesis approach was applied to ...(−)‐maoelactone A (1) and oridonin (2) for the discovery of anti‐SARS‐CoV‐2 agents. The Wolff rearrangement/lactonization cascade (WRLC) reaction was developed to construct the unprecedented maoelactone‐type scaffold during semisynthesis of 1. Further mechanistic study suggested a concerted mechanism for Wolff rearrangement and a water‐assisted stepwise process for lactonization. The WRLC reaction then enabled the creation of a novel family by assembly of the maoelactone‐type scaffold and the pharmacophore of 2, whereby one derivative inhibited SARS‐CoV‐2 replication in HPA EpiC cells with a low EC50 value (19±1 nM) and a high TI value (>1000), both values better than those of remdesivir.
A pharmacophore‐oriented semisynthesis (POSS) approach was applied to (−)‐maoelactone A (1) and oridonin (2) for the discovery of anti‐SARS‐CoV‐2 agents. A Wolff rearrangement/lactonization cascade (WRLC) was developed to install the unprecedented scaffold during semisynthesis of 1. Further assembly of the pharmacophore of 1 and scaffold of 2 by WRLC reaction led to the discovery of a potential anti‐SARS‐CoV‐2 agent with EC50 at 19 nM.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Cancer‐associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer‐associated MSCs (LC‐MSCs) and hepatocellular ...carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC‐MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC‐MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC‐MSCs compared with liver normal MSCs (LN‐MSCs) from adjacent cancer‐free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC‐MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)‐155 in HCC cells was significantly up‐regulated by coculture with LC‐MSCs and by S100A4 ectopic overexpression. The invasion‐promoting effects of S100A4 were significantly attenuated by a miR‐155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR‐155 expression in HCC cells. We demonstrate that S100A4 secreted from LC‐MSCs promotes the expression of miR‐155, which mediates the down‐regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. Conclusion: S100A4 secreted from LC‐MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Energy plays an important role in a fast‐paced modern society. With the depletion of fossil energy, effective utilization of solar energy is getting increasingly urgent. Thermal energy ...storage is an inevitable choice for effective utilization of renewable energy sources. As one of the most promising renewable energy sources, solar energy is inexhaustible. But it has some shortcomings such as instability and intermittency, affected by time, climate, and geographical location. Thermal energy storage technology, which can effectively reduce the cost of concentrated solar power generation, plays a crucial role in bridging the gap between energy supply and demand. In addition, thermal energy storage subsystem can improve performance and reliability of the whole energy system. According to different principles, thermal storage technology is generally classified as sensible heat storage, latent heat storage, and thermochemical energy storage. Most solar thermal power generation systems, currently demonstrated and operated in the world, adopt the method of sensible thermal energy storage. In contrast, thermochemical energy storage is a relatively new concept, which is still in the stage of basic test and verification. Thermochemical energy storage technology stores and releases energy through endothermic and exothermic reversible reactions. A closed system with separated reactants and products, in theory, can store energy indefinitely. The main thermochemical energy storage systems include redox system, metal hydride system, carbonate decomposition system, ammonia decomposition system, methane reforming system, and inorganic hydroxide system.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Fully reduced polyoxometalates are predicted to give rise to a broad and strong absorption spectrum, suitable energy levels, and unparalleled electronic and optical properties. However, they are not ...available to date. Here, an unprecedented fully reduced polyoxomolybdate cluster, namely Na
Mo
O
(OH)
·19H
O {Mo
}, was successfully designed and obtained under hydrothermal conditions, which is rare and is the largest fully reduced polyoxometalate reported so far. The Mo
molecule describes one Keggin {ε-Mo
} encapsulated in an unprecedented {Mo
} cage, giving rise to a double truncated tetrahedron quasi-nesting architecture, which is further face-capped by another four {Mo
} tripods. Its crystalline stability in air, solvent tolerance, and photosensitivity were all shown. As a cheap and robust molecular light-absorber model possessing wide light absorption, Mo
was applied to build a co-sensitized solar cell photoelectronic device along with N719 dyes and the optimal power conversion efficiency was 28% higher than that of single-dye sensitization. These results show that Mo
polyoxometalate could serve as an ideal model for the design and synthesis of all-inorganic molecular light-absorbers for other light-driven processes in the future.
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IJS, KILJ, NUK, UL, UM, UPUK
Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The induction of ACE2 expression may serve as a strategy by ...SARS-CoV-2 to facilitate its propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. Using 45 different luciferase reporters, the transcription factors SP1 and HNF4α were found to positively and negatively regulate ACE2 expression, respectively, at the transcriptional level in human lung epithelial cells (HPAEpiCs). SARS-CoV-2 infection increased the transcriptional activity of SP1 while inhibiting that of HNF4α. The PI3K/AKT signaling pathway, activated by SARS-CoV-2 infection, served as a crucial regulatory node, inducing ACE2 expression by enhancing SP1 phosphorylation-a marker of its activity-and reducing the nuclear localization of HNF4α. However, colchicine treatment inhibited the PI3K/AKT signaling pathway, thereby suppressing ACE2 expression. In Syrian hamsters (
) infected with SARS-CoV-2, inhibition of SP1 by either mithramycin A or colchicine resulted in reduced viral replication and tissue injury. In summary, our study uncovers a novel function of SP1 in the regulation of ACE2 expression and identifies SP1 as a potential target to reduce SARS-CoV-2 infection.
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