The Synthesis of Urolithins and Their Derivatives and the Modes of Antitumor Action.

Urolithins are microbial metabolites derived from berries and pomegranate fruits, which display anti-inflammatory, anti-oxidative, and anti-aging activities. There are eight natural urolithins (urolithin A-E, M5, M6 and M7) isolated by now. Structurally, urolithins are phenolic compounds and belong to 6H-dibenzo[b,d]pyran-6-one. They have drawn considerable attention because of their vast range of biological activities and health benefits. Recent studies also suggest that they possess anti-SARS-CoV-2 and anticancer effects. In this article, the recent advances on the synthesis of urolithins and their derivatives from 2015 to 2021 are reviewed. To improve or overcome the solubility and metabolism stability issues, the modifications of urolithins are mainly centered on the hydroxy group and lactone group, and some compounds are showing promising results and potential for further study. The possible modes of antitumor action of urolithin are also discussed. Several signaling pathways, including PI3K-Akt, Wnt/ß-catenin pathways, and multiple receptors (aryl hydrocarbon receptor, estrogen and androgen receptors) and enzymes (tyrosinase and lactate dehydrogenase) are involved in the antitumor activity of urolithins.

Therapeutic prospects of ceRNAs in COVID-19

Since the end of 2019, COVID-19 caused by SARS-CoV-2 has spread worldwide, and the understanding of the new coronavirus is in a preliminary stage. Currently, immunotherapy, cell therapy, antiviral therapy, and Chinese herbal medicine have been applied in the clinical treatment of the new coronavirus;however, more efficient and safe drugs to control the progress of the new coronavirus are needed. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) may provide new therapeutic targets for novel coronavirus treatments. The first aim of this paper is to review research progress on COVID-19 in the respiratory, immune, digestive, circulatory, urinary, reproductive, and nervous systems. The second aim is to review the body systems and potential therapeutic targets of lncRNAs, miRNAs, and circRNAs in patients with COVID-19. The current research on competing endogenous RNA (ceRNA) (lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA) in SARS-CoV-2 is summarized. Finally, we predict the possible therapeutic targets of four lncRNAs, MALAT1, NEAT1, TUG1, and GAS5, in COVID-19. Importantly, the role of PTEN gene in the ceRNA network predicted by lncRNA MALAT1 and lncRNA TUG1 may help in the discovery and clinical treatment of effective drugs for COVID-19.

The effect of COVID-19 restrictions on atmospheric new particle formation in Beijing

During the COVID-19 lockdown, the dramatic reduction of anthropogenic emissions provided a unique opportunity to investigate the effects of reduced anthropogenic activity and primary emissions on atmospheric chemical processes and the consequent formation of secondary pollutants. Here, we utilize comprehensive observations to examine the response of atmospheric new particle formation (NPF) to the changes in the atmospheric chemical cocktail. We find that the main clustering process was unaffected by the drastically reduced traffic emissions, and the formation rate of 1.5 nm particles remained unaltered. However, particle survival probability was enhanced due to an increased particle growth rate (GR) during the lockdown period, explaining the enhanced NPF activity in earlier studies. For GR at 1.5–3 nm, sulfuric acid (SA) was the main contributor at high temperatures, whilst there were unaccounted contributing vapors at low temperatures. For GR at 3–7 and 7–15 nm, oxygenated organic molecules (OOMs) played a major role. Surprisingly, OOM composition and volatility were insensitive to the large change of atmospheric NOx concentration;instead the associated high particle growth rates and high OOM concentration during the lockdown period were mostly caused by the enhanced atmospheric oxidative capacity. Overall, our findings suggest a limited role of traffic emissions in NPF.

Theoretical Study of the Molecular Mechanism of Maxingyigan Decoction Against COVID-19: Network Pharmacology-based Strategy.

AIM AND OBJECTIVE: Maxingyigan (MXYG) decoction is a traditional Chinese medicine (TCM) prescription. However, how MXYG acts against coronavirus disease 2019 (COVID-19) is not known. We investigated the active ingredients and the therapeutic targets of MXYG decoction against COVID-19. METHODS: A network pharmacology strategy involving drug-likeness evaluation, prediction of oral bioavailability, network analyses, and virtual molecular docking was used to predict the mechanism of action of MXYG against COVID-19. RESULTS: Thirty-three core COVID-19-related targets were identified from 1023 gene targets through analyses of protein-protein interactions. Eighty-six active ingredients of MXYG decoction hit by 19 therapeutic targets were screened out by analyses of a compound-compound target network. Via network topology, three "hub" gene targets (interleukin (IL-6), caspase-3, IL-4) and three key components (quercetin, formononetin, luteolin) were recognized and verified by molecular docking. Compared with control compounds (ribavirin, arbidol), the docking score of quercetin to the IL-6 receptor was highest, with a score of 5. Furthermore, the scores of three key components to SARS-CoV-2 are large as 4, 5, and 5, respectively, which are even better than those of ribavirin at 3. Bioinformatics analyses revealed that MXYG could prevent and treat COVID-19 through anti-inflammatory and immunity-based actions involving activation of T cells, lymphocytes, and leukocytes, as well as cytokine-cytokine-receptor interaction, and chemokine signaling pathways. CONCLUSION: The hub genes of COVID-19 helped to reveal the underlying pathogenesis and therapeutic targets of COVID-19. This study represents the first report on the molecular mechanism of MXYG decoction against COVID-19.