Table_1_Lockdown Policies, Economic Support, and Mental Health: Evidence From the COVID-19 Pandemic in United States.DOCX

During the COVID-19 pandemic, various lockdown policies were put in place by the governments in different countries and different levels, which effectively curbed the spread of the virus, but also cause substantial damage to the mental health of local residents. We use statistics provided by the Household Pulse Survey and OxCGRT between 23 April 2020 and 30 August 2021 to analyze the impact of lockdown on overall mental health levels in US states during the COVID-19 pandemic at the macro level. The results show that the lockdown policies implemented by the state governments lead to a deterioration in psychological conditions, and this relationship varies to some extent depending on the level of high-quality economic support, that the state governments implement to alleviate the symptoms of depression and anxiety associated with the lockdown. Therefore, we argue that although lockdown policies are necessary during the COVID-19 pandemic, further government efforts are needed to give high-quality economic and mental health support to mitigate the negative effects of lockdown on mental health.</p

Analysis of Stability of Transcription System in Octane Media by Molecular Dynamics Simulation

Enzymatic catalysis in nonaqueous environments has many advantages over that in aqueous solution. However, structural stability and flexibility of enzymes restrict their applications in nonaqueous environments. It was proposed that nonaqueous media decrease the flexibility of enzymes, resulting in their reduced activity. There is little detailed information to clarify the impact of nonaqueous solvents on the structure and flexibility of enzymes at molecular level. In this work, by using the molecular dynamics simulation technology, we placed an entire transcription system in organic solvent to investigate the effects of nonpolar solvent on an enzyme. A small transcription machine, T7 RNA polymerase (T7 RNAP), was used as model enzyme to conduct this study. We constructed two models with the T7 RNAP complex solvated in organic solvent. The first one is to solvate the T7 RNAP complex in pure octane directly. Our observation shows that T7 RNAP suffers serious structural deterioration in octane, especially in the active site, that the original correct binding of the substrate was completely destroyed. The structural deterioration may seriously affect the activity of T7 RNAP. Another model was built by pulling the transcription system from water into octane. It was observed that a small portion of water with some ions was carried into the organic media and coated on the surface of the complex. The water layer forms a microaqueous solution environment that plays an important role in protecting the internal structure of the transcription system. However, the flexibility of some key residues was reduced in the simulation time. It is deduced that a higher temperature is necessary to improve its activity in nonaqueous solvents. Our results are in good agreement with those reported in the literature. It is expected that our research could provide valuable information for the application of enzymes in nonaqueous environments

Discovery of Potent and Selective CB2 Agonists Utilizing a Function-Based Computational Screening Protocol

Nowadays, the identification of agonists and antagonists represents a great challenge in computer-aided drug design. In this work, we developed a computational protocol enabling us to design/screen novel chemicals that are likely to serve as selective CB2 agonists. The principle of this protocol is that by calculating the ligand–residue interaction profile (LRIP) of a ligand binding to a specific target, the agonist–antagonist function of a compound is then able to be determined after statistical analysis and free energy calculations. This computational protocol was successfully applied in CB2 agonist development starting from a lead compound, and a success rate of 70% was achieved. The functions of the synthesized derivatives were determined by in vitro functional assays. Moreover, the identified potent CB2 agonists and antagonists strongly interact with the key residues identified using the already known potent CB2 agonists/antagonists. The analysis of the interaction profile of compound 6, a potent agonist, showed strong interactions with F2.61, I186, and F2.64, while compound 39, a potent antagonist, showed strong interactions with L17, W6.48, V6.51, and C7.42. Still, some residues including V3.32, T3.33, S7.39, F183, W5.43, and I3.29 are hotspots for both CB2 agonists and antagonists. More significantly, we identified three hotspot residues in the loop, including I186 for agonists, L17 for antagonists, and F183 for both. These hotspot residues are typically not considered in CB1/CB2 rational ligand design. In conclusion, LRIP is a useful concept in rationally designing a compound to possess a certain function

Photoredox-Catalyzed Redox-Neutral Decarboxylative C–H Acylations of Coumarins with α‑Keto Acid

A novel and green photocatalytic strategy for the synthesis of C-4-acylated coumarins with α-keto acids and 3-nitrocoumarin has been developed. This operationally simple protocol works under mild reaction conditions, providing convenient access to 4-acyl coumarin derivatives. The control experimental results showed that the nitro radical produced by the cleavage of the C–N bond acts as an electron acceptor to complete the photocatalytic cycle, achieving a redox-neutral reaction

Visible-Light-Induced Regioselective Radical Oxo-Amination of Alkenes with O₂ as the Oxygen Source

An efficient and novel visible-light-induced oxo-amination of terminal alkenes for the construction of α-amino ketones with easily accessible and green O2 as the oxygen source has been developed. The transformation possesses the advantages of operational simplicity, a broad substrate scope, high atom economy, and mild reaction conditions. The mechanistic studies reveal that an energy transfer process probably occurs in the initial stage, and the reaction proceeds via β-scission of the alkoxyl radical species

Discovery of Potent and Selective CB2 Agonists Utilizing a Function-Based Computational Screening Protocol

Nowadays, the identification of agonists and antagonists represents a great challenge in computer-aided drug design. In this work, we developed a computational protocol enabling us to design/screen novel chemicals that are likely to serve as selective CB2 agonists. The principle of this protocol is that by calculating the ligand–residue interaction profile (LRIP) of a ligand binding to a specific target, the agonist–antagonist function of a compound is then able to be determined after statistical analysis and free energy calculations. This computational protocol was successfully applied in CB2 agonist development starting from a lead compound, and a success rate of 70% was achieved. The functions of the synthesized derivatives were determined by in vitro functional assays. Moreover, the identified potent CB2 agonists and antagonists strongly interact with the key residues identified using the already known potent CB2 agonists/antagonists. The analysis of the interaction profile of compound 6, a potent agonist, showed strong interactions with F2.61, I186, and F2.64, while compound 39, a potent antagonist, showed strong interactions with L17, W6.48, V6.51, and C7.42. Still, some residues including V3.32, T3.33, S7.39, F183, W5.43, and I3.29 are hotspots for both CB2 agonists and antagonists. More significantly, we identified three hotspot residues in the loop, including I186 for agonists, L17 for antagonists, and F183 for both. These hotspot residues are typically not considered in CB1/CB2 rational ligand design. In conclusion, LRIP is a useful concept in rationally designing a compound to possess a certain function

Integrative Analyses of Metabolomes and Transcriptomes Provide Insights into Flavonoid Variation in Grape Berries

Flavonoids in grapes contribute the quality of the berry, but the flavonoid diversity and the regulatory networks underlying the variation require a further investigation. In this study, we integrated multi-omics data to systematically explore the global metabolic and transcriptional profiles in the skins and pulps of three grape cultivars. The results revealed large-scale differences involved in the flavonoid metabolic pathway. A total of 133 flavonoids, including flavone and flavone C-glycosides, were identified. Beyond the visible differences of anthocyanins, there was large variation in other sub-branched flavonoids, most of which were positively correlated with anthocyanins in grapes. The expressions of most flavonoid biosynthetic genes and the major regulators MYBA1 were strongly consistent with the changes in flavonoids. Integrative analysis identified two novel transcription factors (MYB24 and MADS5) and two ubiquitin proteins (RHA2) as promising regulatory candidates for flavonoid biosynthesis in grapes. Further verification in various grape accessions indicated that five major genes including flavonol 3′5′-hydroxylase (F3′5′H), UDP-glucose:flavonoid 3-O-glycosyl-transferase, anthocyanin O-methyltransferase, acyltransferase (3AT), and glutathione S-transferase (GST4) controlled flavonoid variation in grape berries. These findings provide valuable information for understanding the mechanism of flavonoid biosynthesis in grape berries and the further development of grape health products

Integrative Analyses of Metabolomes and Transcriptomes Provide Insights into Flavonoid Variation in Grape Berries

Flavonoids in grapes contribute the quality of the berry, but the flavonoid diversity and the regulatory networks underlying the variation require a further investigation. In this study, we integrated multi-omics data to systematically explore the global metabolic and transcriptional profiles in the skins and pulps of three grape cultivars. The results revealed large-scale differences involved in the flavonoid metabolic pathway. A total of 133 flavonoids, including flavone and flavone C-glycosides, were identified. Beyond the visible differences of anthocyanins, there was large variation in other sub-branched flavonoids, most of which were positively correlated with anthocyanins in grapes. The expressions of most flavonoid biosynthetic genes and the major regulators MYBA1 were strongly consistent with the changes in flavonoids. Integrative analysis identified two novel transcription factors (MYB24 and MADS5) and two ubiquitin proteins (RHA2) as promising regulatory candidates for flavonoid biosynthesis in grapes. Further verification in various grape accessions indicated that five major genes including flavonol 3′5′-hydroxylase (F3′5′H), UDP-glucose:flavonoid 3-O-glycosyl-transferase, anthocyanin O-methyltransferase, acyltransferase (3AT), and glutathione S-transferase (GST4) controlled flavonoid variation in grape berries. These findings provide valuable information for understanding the mechanism of flavonoid biosynthesis in grape berries and the further development of grape health products

Integrative Analyses of Metabolomes and Transcriptomes Provide Insights into Flavonoid Variation in Grape Berries

Flavonoids in grapes contribute the quality of the berry, but the flavonoid diversity and the regulatory networks underlying the variation require a further investigation. In this study, we integrated multi-omics data to systematically explore the global metabolic and transcriptional profiles in the skins and pulps of three grape cultivars. The results revealed large-scale differences involved in the flavonoid metabolic pathway. A total of 133 flavonoids, including flavone and flavone C-glycosides, were identified. Beyond the visible differences of anthocyanins, there was large variation in other sub-branched flavonoids, most of which were positively correlated with anthocyanins in grapes. The expressions of most flavonoid biosynthetic genes and the major regulators MYBA1 were strongly consistent with the changes in flavonoids. Integrative analysis identified two novel transcription factors (MYB24 and MADS5) and two ubiquitin proteins (RHA2) as promising regulatory candidates for flavonoid biosynthesis in grapes. Further verification in various grape accessions indicated that five major genes including flavonol 3′5′-hydroxylase (F3′5′H), UDP-glucose:flavonoid 3-O-glycosyl-transferase, anthocyanin O-methyltransferase, acyltransferase (3AT), and glutathione S-transferase (GST4) controlled flavonoid variation in grape berries. These findings provide valuable information for understanding the mechanism of flavonoid biosynthesis in grape berries and the further development of grape health products

Integrative Analyses of Metabolomes and Transcriptomes Provide Insights into Flavonoid Variation in Grape Berries

Flavonoids in grapes contribute the quality of the berry, but the flavonoid diversity and the regulatory networks underlying the variation require a further investigation. In this study, we integrated multi-omics data to systematically explore the global metabolic and transcriptional profiles in the skins and pulps of three grape cultivars. The results revealed large-scale differences involved in the flavonoid metabolic pathway. A total of 133 flavonoids, including flavone and flavone C-glycosides, were identified. Beyond the visible differences of anthocyanins, there was large variation in other sub-branched flavonoids, most of which were positively correlated with anthocyanins in grapes. The expressions of most flavonoid biosynthetic genes and the major regulators MYBA1 were strongly consistent with the changes in flavonoids. Integrative analysis identified two novel transcription factors (MYB24 and MADS5) and two ubiquitin proteins (RHA2) as promising regulatory candidates for flavonoid biosynthesis in grapes. Further verification in various grape accessions indicated that five major genes including flavonol 3′5′-hydroxylase (F3′5′H), UDP-glucose:flavonoid 3-O-glycosyl-transferase, anthocyanin O-methyltransferase, acyltransferase (3AT), and glutathione S-transferase (GST4) controlled flavonoid variation in grape berries. These findings provide valuable information for understanding the mechanism of flavonoid biosynthesis in grape berries and the further development of grape health products