Water, as a green reaction medium, is safe, non-toxic, and rich in reserves on Earth, while visible light represents a renewable, clean, and abundant energy source. Organic transformations carried ...out under the irradiation of visible light in water are undoubtedly more attractive, and are in line with the concept of "green chemistry" to effectively minimize the environmental impact of chemical synthesis. This review focuses on the recent progress in visible-light-mediated organic transformations in water, and the related mechanisms are also discussed. Although great achievements have been made, they are just the tip of the iceberg and there is still great room for improvement. This review will facilitate the understanding of visible-light-mediated organic transformations in water and further stimulate the advancement of more novel relevant strategies.
Water is a green reaction medium, while visible light represents a renewable, clean, and abundant energy source. The recent advances in visible-light-mediated organic transformations in water are summarized.
Radical cascade cyclization of β,γ‐unsaturated hydrazones/oximes has recently emerged as an efficient and powerful protocol for the construction of diverse and valuable functionalized pyrazolines and ...isoxazolines. In this review, three catalytic ways of radical cascade cyclization of β,γ‐unsaturated hydrazones/oximes are summarized and classified; these are transition‐metal‐catalyzed systems, transition‐metal‐free systems, and photo‐/electrocatalytic systems, respectively. Through these methods, various functional groups are installed on the pyrazoline and isoxazoline skeletons to enrich the small organic molecule library.
A metal‐free visible‐light‐induced cyclization procedure was developed for the rapid synthesis of perfluoroalkyl‐substituted benzimidazo2,1‐aisoquinolin‐6(5H)‐ones and perfluoroalkyl‐substituted ...indolo2,1‐aisoquinolin‐6(5H)‐ones under mild reaction conditions. In this procedure, the formation of electron‐donor‐acceptor (EDA) complex is critical for the visible‐light promoted process to avoid the utilization of external photocatalysts.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmitted through the respiratory route, but potential extra-respiratory routes of SARS-CoV-2 transmission remain uncertain. ...Here we inoculated five rhesus macaques with 1 × 10
TCID
of SARS-CoV-2 conjunctivally (CJ), intratracheally (IT), and intragastrically (IG). Nasal and throat swabs collected from CJ and IT had detectable viral RNA at 1-7 days post-inoculation (dpi). Viral RNA was detected in anal swabs from only the IT group at 1-7 dpi. Viral RNA was undetectable in tested swabs and tissues after intragastric inoculation. The CJ infected animal had a higher viral load in the nasolacrimal system than the IT infected animal but also showed mild interstitial pneumonia, suggesting distinct virus distributions. This study shows that infection via the conjunctival route is possible in non-human primates; further studies are necessary to compare the relative risk and pathogenesis of infection through these different routes in more detail.
Silent hypoxia has emerged as a unique feature of coronavirus disease 2019 (COVID-19). In this study, we show that mucins are accumulated in the bronchoalveolar lavage fluid (BALF) of COVID-19 ...patients and are upregulated in the lungs of severe respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected mice and macaques. We find that induction of either interferon (IFN)-β or IFN-γ upon SARS-CoV-2 infection results in activation of aryl hydrocarbon receptor (AhR) signaling through an IDO-Kyn-dependent pathway, leading to transcriptional upregulation of the expression of mucins, both the secreted and membrane-bound, in alveolar epithelial cells. Consequently, accumulated alveolar mucus affects the blood-gas barrier, thus inducing hypoxia and diminishing lung capacity, which can be reversed by blocking AhR activity. These findings potentially explain the silent hypoxia formation in COVID-19 patients, and suggest a possible intervention strategy by targeting the AhR pathway.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern
. ...Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)
. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.
Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It is unclear whether ...convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.
The cyano group is a valuable and readily available functional group for the preparation of various functional groups, such as amines, carboxylic acids, and ketones. In recent decades, the radical ...cascade reaction has emerged as a versatile tool to prepare a large variety of functional molecules. The application of the cyano group as a radical acceptor in cascade reactions provides diverse opportunities for the convenient construction of various important heterocycles and carbocycles. Such synthetic strategies will open new ways for the rapid buildup of molecular complexity. The focus of this review is the summary of the dynamic field of radical cascade processes using the cyano group as a radical acceptor, which has not been well documented so far.
Circular RNAs (circRNAs) are a novel type of endogenous RNAs featuring stable structure and high tissue-specific expression. Recently, accumulating evidence has revealed that aberrant circRNAs ...expression plays important roles in carcinogenesis and tumor progression. However, the expression pattern and biological function of circRNAs in non small cell lung cancer (NSCLC) remain largely unknown. Therefore, the purpose of this study was to clarify the possible role of one of typical circRNAs, circRNA_100876 in NSCLC and to define its prognostic value in NSCLC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circRNA_100876 in tumor tissues and their adjacent nontumorous tissues in 101 patients with NSCLC. We found that the expression level of circRNA_100876 was significantly elevated in NSCLC tissues when compared with their adjacent nontumorous tissues (P=0.000). Moreover, there was a close correlation between the circRNA_100876 up-regulation expression and lymph node metastasis (P=0.001) and tumor staging (P=0.001) in NSCLC. In addition, Kaplan-Meier survival analysis demonstrated that the overall survival time of NSCLC patients with high circRNA_100876 expression was significantly shorter than those patients with low circRNA_100876 expression (P=0.000). In conclusion, our findings indicate that circRNA_100876 is closely related to the carcinogenesis of NSCLC and it might be served as a potential prognostic biomarker and therapeutic target for NSCLC.
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The present study aimed to evaluate the anti-colitis effect and underlying mechanisms of cardamonin, a natural flavone isolated from Alpinia katsumadai Hayata. The results showed that ...oral cardamonin significantly inhibited dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice, evidenced by improvement of disease activity index scores, myeloperoxidase activity, length shortening and histopathological changes of colons. A rectal administration of cardamonin also exhibited marked anti-colitis effect, suggesting that oral cardamonin might function in a prototype form. Cardamonin down-regulated levels of IL-1β, TNF-α, IL-6, NLRP3, cleaved caspase-1, ASC, cleaved IL-1β in colons of colitis mice. In vitro, cardamonin inhibited NLRP3 inflammasome activation in THP-1 and bone marrow-derived macrophages. It acted as an AhR activator, enhanced dissociation of AhR/HSP90 complexes, association of AhR/ARNT complexes, AhR nuclear translocation, XRE reporter gene activity, and AhR/ARNT/XRE DNA binding activity in THP-1 cells. The AhR antagonist CH223191 obviously abolished NLRP3 inflammasome activation inhibited by cardamonin. Furthermore, cardamonin elevated levels of Nrf2 and its target genes NQO1, Trx1, SOD2, HO-1, and the effect on NQO1 was the most obvious. The relationship of cardamonin-adjusted AhR activation, expressions of Nrf2 and NQO1, and NLRP3 inflammasome activation was confirmed by using CH223191, siAhR, ML385 and siNQO1, respectively. Finally, CH223191 was shown to abolish amelioration of cardamonin on DSS- and TNBS-induced colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 and NQO1 levels in colons. Taken together, cardamonin ameliorated colitis in mice through the activation of AhR/Nrf2/NQO1 pathway and consequent inhibition of NLRP3 inflammasome activation.
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