Ligand-Controlled, Nickel-Catalyzed Stereodivergent Construction of 1,3-Nonadjacent Stereocenters.

In contrast to the asymmetric synthesis of molecules with a single stereocenter or 1,2-adjacent stereocenters, the simultaneous construction of acyclic 1,3-nonadjacent stereocenters via a single catalyst in an enantioselective and diastereoselective manner remains a formidable challenge. Here, we demonstrate the enantioselective and diastereodivergent construction of 1,3-nonadjacent stereocenters through Ni-catalyzed reductive cyclization/cross-coupling of alkene-tethered aryl bromides and α-bromoamides, which represents the major remaining stereochemical challenge of cyclization/difunctionalization of alkenes. Using Ming-Phos as ligand, a diverse set of oxindoles containing 1,3-nonadjacent stereocenters were obtained with high levels of enantio- and diastereoselectivity. Mechanistic experiments and density functional theory calculations indicate that magnesium salt plays a key role in controlling the diastereoselectivity. Furthermore, another set of complementary stereoisomeric products were constructed from the same set of starting materials using Ph-Phox as ligand.

The Extract of Acanthopanacis Cortex Relieves the Depression-Like Behavior and Modulates IL-17 Signaling in Chronic Mild Stress-Induced Depressive Mice.

Background: Acanthopanacis Cortex (AC) is a valuable Chinese medicine, which exerts beneficial effects on anti-fatigue, anti-stress, and inflammatory modulation in the periphery. However, the central nervous system (CNS) function of AC has not been clearly illustrated. As communication between the peripheral immune system and the CNS converges, it promotes a heightened neuroinflammatory environment that contributes to depression. We investigated the effect of AC against depression through neuroinflammatory modulation. Methods: Network pharmacology was used to screen for target compounds and pathways. Mice with CMS-induced depression were used to evaluate the efficacy of AC against depression. Behavioral studies and detection of neurotransmitters, neurotrophic factors, and pro-inflammatory cytokines were performed. The IL-17 signaling cascade was involved to further investigate the underlying mechanism of AC against depression. Results: Twenty-five components were screened by network pharmacology and the IL-17 mediated signaling pathway was associated with the antidepressant action of AC. This herb had a beneficial effect on CMS-induced depressive mice, including improvements in depressive behavior, modulation of neurotransmitter levels, neurotrophic factors, and pro-inflammatory cytokines. Conclusions: Our results revealed that AC exhibits effects on anti-depression and one of the mechanisms was mediated by neuroinflammatory modulation.

Alpha-Asarone modulates kynurenine disposal in muscle and mediates resilience to stress-induced depression via PGC-1α induction.

INTRODUCTION: Kynurenine (KYN) accumulation in periphery induces brain injury, responsible for depression. α-Asarone is a simple phenylpropanoids that exerts beneficial effects on central nervous system. However, the effect of α-asarone on periphery is unexplored. AIMS: Here, we investigated its protective role against depression from the aspect of KYN metabolism in skeletal muscle. METHODS: The antidepressant effects of α-asarone were evaluated in chronic mild stress (CMS) and muscle-specific PGC-1α-deficient mice. The effects of KYN metabolism were determined in mice and C2C12 myoblasts. RESULTS: α-Asarone exerted antidepressant effects in CMS and KYN-challenged mice via modulating KYN metabolism. In myoblasts, α-asarone regulated PGC-1α induction via cAMP/CREB signaling and upregulated KYN aminotransferases (KATs) to increase KYN clearance in a manner dependent on PGC-1α. KAT function is coupled with malate-aspartate shuttle (MAS), while α-asarone combated oxidative stress to protect MAS and mitochondrial integrity by raising the NAD+ /NADH ratio, ensuring effective KYN disposal. In support, the antidepressant effect of α-asarone was diminished by muscle-specific PGC-1α deficient mice subjected to KYN challenge. CONCLUSION: KATs coupled with MAS to clear KYN in muscle. α-Asarone increased PGC-1α induction and promoted KYN disposal in muscle, suggesting that protection of mitochondria is a way for pharmacological intervention to depression.

Direct acylation and alkynylation of hydrocarbons via synergistic decatungstate photo-HAT/nickel catalysis.

Herein, we describe a protocol for the direct and selective acylation and alkynylation of the C(sp3)-H bonds of saturated hydrocarbons by synergistic decatungstate photo-HAT and nickel catalysis. This method, using cheap and easy-to-synthesize TBADT as a HAT photocatalyst, exhibits excellent site selectivity. A wide variety of high-value ketones, amides, esters, and diverse alkynes can be efficiently constructed from abundant hydrocarbon feedstocks.

High-Performance, Free-Standing Symmetric Hybrid Membranes for Osmotic Separation.

The internal concentration polarization (ICP) of asymmetric osmotic membranes with support layers greatly reduced membrane water permeability, therefore compromising membrane performance. In this study, a series of free-standing symmetric hybrid forward osmosis (FO) membranes without experiencing ICP were fabricated by covalently linking metal-organic framework (MOF) nanofillers with a polymer matrix. Owing to the introduction of MOFs, which allow only water permeation but reject salts by steric hindrance, the prepared hybrid membranes could approach the empirical permeability-selectivity trade-off. The optimized hybrid membrane displayed an outstanding water/Na2SO4 selectivity of ∼1208.4 L mol-1, compared with that of conventional membranes of ∼375.6 L mol-1. Additionally, the fabricated hybrid membranes showed excellent mechanical robustness, maintaining structural integrity during the long-term FO separation of high-salinity solution. This work provides an effective methodology to fabricate high-performance, symmetric MOF-based membranes for osmotic separation processes such as seawater desalination and water purification.

High hydrostatic pressure inactivation of murine norovirus and human noroviruses on green onions and in salsa.

In this study, high hydrostatic pressure (HHP) was evaluated as an intervention for human noroviruses (HuNoVs) in green onions and salsa. To determine the effect of water during HHP treatment on virus inactivation, a HuNoV surrogate, murine norovirus 1 (MNV-1), was inoculated onto green onions and then HHP-treated at 350MPa with or without water at 4 or 20°C. The presence of water enhanced HHP inactivation of MNV-1 on green onions at 4°C but not at 20°C. To test the temperature effect on HHP inactivation of MNV-1, inoculated green onions were HHP-treated at 300MPa at 1, 4 and 10°C. As the temperature decreased, MNV-1 became more sensitive to HHP treatment. HHP inactivation curves of MNV-1 on green onions and salsa were obtained at 300 or 350MPa for 0.5-3min at 1°C. All three inactivation curves showed a linear relationship between log reduction of MNV-1 and time. D values of HHP inactivation of MNV-1 on green onions were 1.10 and 0.61min at 300 and 350MPa, respectively. The D value of HHP inactivation of MNV-1 in salsa at 300MPa was 0.63min. HHP inactivation of HuNoV GI.1 and GII.4 on green onions and salsa was also conducted. To achieve >3 log reduction of HuNoV GI.1, HHP treatments for 2min at 1°C should be conducted at 600MPa and 500MPa for green onions and salsa, respectively. To achieve >3 log reduction of HuNoV GII.4, HHP treatments for 2min at 1°C should be conducted at 500MPa and 300MPa for green onions and salsa, respectively.

Application of water-assisted ultraviolet light processing on the inactivation of murine norovirus on blueberries.

In this study, a novel set-up using water-assisted UV processing was developed and evaluated for its decontamination efficacy against murine norovirus (MNV-1) inoculated on fresh blueberries for both small and large-scale experimental setups. Blueberries were skin-inoculated with MNV-1 and treated for 1-5 min with UV directly (dry UV) or immersed in agitated water during UV treatment (water-assisted UV). The effect of the presence of 2% (v/v) blueberry juice or 5% crushed blueberries (w/w) in wash water was also evaluated. Results showed that water-assisted UV treatment generally showed higher efficacies than dry UV treatment. With 12,000 J/m(2) UV treatment in small-scale setup, MNV reductions of >4.32- and 2.48-log were achieved by water-assisted UV and dry UV treatments, respectively. Water-assisted UV showed similar inactivating efficacy as 10-ppm chlorine wash. No virus was detected in wash water after UV treatment or chlorine wash. MNV-1 was more easily killed on skin-inoculated blueberries compared with calyx-inoculated berries. When clear water was used as wash water in the large-scale setup, water-assisted UV treatment (UV dose of 12,000 J/m(2)) resulted in >3.20 log and 1.81 log MNV-1 reductions for skin- and calyx-inoculated berries, respectively. The presence of 2% blueberry juice in wash water decreased the decontamination efficacy of water-assisted UV and chlorine washing treatments. To improve the inactivation efficacy, the effect of combining water-assisted UV treatment with chlorine washing was also evaluated. The combined treatment had better or similar inactivation efficacy compared to water-assisted UV treatment and chlorine washing alone. Findings of this study suggest that water-assisted UV treatment could be used as an alternative to chlorine washing for blueberries and potentially for other fresh produce.

Inactivation of Escherichia Coli O157:H7 and Salmonella Enterica on Blueberries in Water Using Ultraviolet Light.

UNLABELLED: Ultraviolet light (UV) has antimicrobial effects, but the shadowing effect has limited its application. In this study, a novel setup using UV processing in agitated water was developed to inactivate Escherichia coli O157:H7 and Salmonella on blueberries. Blueberries were dip- or spot-inoculated with E. coli or Salmonella. Blueberries inoculated with E. coli were treated for 2 to 10 min with UV directly (dry UV) or immersed in agitated water during UV treatment (wet UV). E. coli was most easily killed on spot-inoculated blueberries with a 5.2-log reduction after 10-min wet UV treatment. Dip-inoculated blueberries were the most difficult to be decontaminated with only 1.6-log reduction after 10-min wet UV treatment. Wet UV treatment generally showed higher efficacies than dry UV treatment, achieving an average of 1.4 log more reduction for spot-inoculated blueberries. For dip-inoculated blueberries, chlorine washing and UV treatments were less effective, achieving <2 log reductions of E. coli. Thus, the efficacy of combinations of wet UV with sodium dodecyl sulfate (SDS), levulinic acid, or chlorine was evaluated. Inoculated blueberries were UV-treated while being immersed in agitated water containing 100 ppm SDS, 0.5% levulinic acid or 10 ppm chlorine. The 3 chemicals did not significantly enhance the wet UV treatment. Findings of this study suggest that UV treatment could be used as an alternative to chlorine washing for blueberries and potentially for other fresh produce. PRACTICAL APPLICATION: A novel UV light system for decontamination of blueberries in water was developed and evaluated. Results demonstrated that the decontamination efficacy of this system was generally as effective as chlorine washing, indicating that it could potentially be used as an alternative to chlorine washing for blueberries and other fresh produce.