Facile Synthesis of Tricyclic 1,2,4-Oxadiazolines-Fused Tetrahydro-Isoquinolines from Oxime Chlorides with 3,4-Dihydroisoquinoline Imines

A mild and efficient strategy for the synthesis of tricyclic 1,2,4-oxadiazolines-fused tetrahydro-isoquinolines derivatives via [3 + 2] cycloaddition reaction is reported. The reactions provided the functionalized tricyclic 1,2,4-oxadiazolines in high yields (up to 96%). This protocol is simple and easy to handle. Moreover, a gram-scale experiment further highlights the synthetic utility. The chemical structure of the product was determined by X-ray single-crystal structure analysis. A possible mechanism for this transformation is proposed to explain the reaction process.     

A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight

Polyphenolic acids are the widely occurring natural products in almost each herbal plant, among which rosmarinic acid (RA, C₁₈H₁₆O₈) is well-known, and is present in over 160 species belonging to many families, especially the Lamiaceae. Aside from this herbal ingredient, dozens of its natural derivatives have also been isolated and characterized from many natural plants. In recent years, with the increasing focus on the natural products as alternative treatments, a large number of pharmacological studies have been carried out to demonstrate the various biological activities of RA such as anti-inflammation, anti-oxidation, anti-diabetes, anti-virus, anti-tumor, neuroprotection, hepatoprotection, etc. In addition, investigations concerning its biosynthesis, extraction, analysis, clinical applications, and pharmacokinetics have also been performed. Although many achievements have been made in various research aspects, there still exist some problems or issues to be answered, especially its toxicity and bioavailability. Thus, we hope that in the case of natural products, the present review can not only provide a comprehensive understanding on RA covering its miscellaneous research fields, but also highlight some of the present issues and future perspectives worth investigating later, in order to help us utilize this polyphenolic acid more efficiently, widely, and safely.     

Development of a ~3He Gas Filling Station at the China Spallation Neutron Source

At the China Spallation Neutron Source(CSNS), we have developed a custom gas-filling station, a glassblowing workshop, and a spin-exchange optical pumping(SEOP) system for producing high-quality ~3He-based neutron spin filter(NSF) cells. The gas-filling station is capable of routinely filling ~3He cells made from GE180 glass of various dimensions, to be used as neutron polarizers and analyzers on beamlines at the CSNS. Performance tests on cells fabricated at our gas-filling station are conducted via neutron transmission and nuclear-magneticresonance measurements, revealing nominal filling pressures, and a saturated ~3He polarization in the region of 80%, with a lifetime of approximately 240 hours. These results demonstrate our ability to produce competitive NSF cells to meet the ever-increasing research needs of the polarized neutron research community.     

Designable assembly of atomically precise Al4O4 cubane supported mesoporous heterometallic architectures

Heterometallic cluster-based framework materials are of interest in terms of both their porous structures and multi-metallic reactivity. However, such materials have not yet been extensively investigated because of difficulties in their synthesis and structural characterization. Herein, we reported the designable synthesis of atomically precise heterometallic cluster-based framework compounds and their application as catalysts in aldol reactions. By using the synergistic coordination protocol, we successfully isolated a broad range of compounds with the general formula, [Al₄M₄O₄(L)₁₂(DABCO)₂] (L = carboxylates; DABCO = 1,4-diazabicyclo[2.2.2]-octane; M²⁺ = Co²⁺, Mn²⁺, Zn²⁺, Fe²⁺, Cd²⁺). The basic heterometallic building blocks contain unprecedented main-group γ-alumina moieties and surrounding unsaturated transition metal centers. Interestingly, the porosity and interpenetration of these frameworks can be rationally regulated through the unprecedented strategy of increment of the metal radius in addition to general introduction of sterically bulky groups on the ligand. Furthermore, these porous materials are effective catalysts for aldol reactions. This work provides a catalytic molecular model platform with accurate molecular bonding between the supporters and catalytically active metal ions.

Mesoporous heterometallic architectures are designed by the incorporation of the Al₄O₄ cubane and interpenetration regulation.     

PTC: Full and Drift Particle Orbit Tracing Code for α Particles in Tokamak Plasmas

Fusion born α particle confinement is one of the most important issues in burning plasmas,such as ITER and CFETR.However,it is extremely complex due to the nonequilibrium characteristics,and multiple temporal and spatial scales coupling with background plasma.A numerical code using particle orbit tracing method(PTC)has been developed to study energetic particle confinement in tokamak plasmas.Both full orbit and drift orbit solvers are implemented to analyze the Larmor radius effects on α particle confinement.The elastic collisions between alpha particles and thermal plasma are calculated by a Monte Carlo method.A triangle mesh in poloidal section is generated for electromagnetic fields expression.Benchmark between PTC and ORBIT has been accomplished for verification.For CFETR burning plasmas,PTC code is used for α particle source and slowing down process calculation in 2D equilibrium.In future work,3D field like toroidal field ripples,Alfven and magnetohydrodynamics instabilities perturbation inducing α particle transport will be analyzed.     

Hepatoprotective Effects of Ixeris chinensis on Nonalcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice: An Integrated Gut Microbiota and Metabolomic Analysis

Ixeris chinensis (Thunb.) Nakai (IC) is a folk medicinal herb used in Mongolian medical clinics for the treatment of hepatitis and fatty liver diseases even though its pharmacological mechanism has not been well characterized. This study investigated the hepatoprotective mechanism of IC on mice with nonalcoholic fatty liver disease (NAFLD) by integrating gut microbiota and metabolomic analysis. A high-fat diet (HFD) was used to develop nonalcoholic fatty liver disease, after which the mice were treated with oral IC (0.5, 1.5 and 3.0 g/kg) for 10 weeks. HFD induced NAFLD and the therapeutic effects were characterized by pathological and histological evaluations, and the serum indicators were analyzed by ELISA. The gut microbial and metabolite profiles were studied by 16S rRNA sequencing and untargeted metabolomic analysis, respectively. The results showed that the administration of IC resulted in significant decreases in body weight; liver index; serum biomarkers such as ALT, TG, and LDL-C; and the liver inflammatory factors IL-1β, IL-6, and TNF-α. The 16S rRNA sequencing results showed that administration of IC extract altered both the composition and abundance of the gut microbiota. Untargeted metabolomic analysis of liver samples detected a total of 212 metabolites, of which 128 were differentially expressed between the HFD and IC group. IC was found to significantly alter the levels of metabolites such as L-glutamic acid, pyridoxal, ornithine, L-aspartic acid, D-proline, and N4-acetylaminobutanal, which are involved in the regulation of glutamine and glutamate, Vitamin B6 metabolism, and arginine and proline metabolic pathways. Correlation analysis indicated that the effects of the IC extract on metabolites were associated with alterations in the abundance of Akkermansiaceae, Lachnospiraceae, and Muribaculaceae. Our study revealed that IC has a potential hepatoprotective effect in NAFLD and that its function might be linked to improvements in the composition of gut microbiota and their metabolites.     

Spider Silk-Improved Quartz-Enhanced Conductance Spectroscopy for Medical Mask Humidity Sensing

Spider silk is one of the hottest biomaterials researched currently, due to its excellent mechanical properties. This work reports a novel humidity sensing platform based on a spider silk-modified quartz tuning fork (SSM-QTF). Since spider silk is a kind of natural moisture-sensitive material, it does not demand additional sensitization. Quartz-enhanced conductance spectroscopy (QECS) was combined with the SSM-QTF to access humidity sensing sensitively. The results indicate that the resonance frequency of the SSM-QTF decreased monotonously with the ambient humidity. The detection sensitivity of the proposed SSM-QTF sensor was 12.7 ppm at 1 min. The SSM-QTF sensor showed good linearity of ~0.99. Using this sensor, we successfully measured the humidity of disposable medical masks for different periods of wearing time. The results showed that even a 20 min wearing time can lead to a >70% humidity in the mask enclosed space. It is suggested that a disposable medical mask should be changed <2 h.     

Characterization of Roasting Time on Sensory Quality,Color, Taste,and Nonvolatile Compounds of Yuan An Yellow Tea

Roasting is crucial for producing Yuan An yellow tea (YAYT) as it substantially affects sensory quality. However, the effect of roasting time on YAYT flavor quality is not clear. To investigate the effect of roasting time on the sensory qualities, chemical components, odor profiles, and metabolic profile of YAYTs produced with 13 min roasting, 16 min roasting, 19 min roasting, 22 min roasting, and 25 min roasting were determined. The YAYTs roasted for 22 min got higher sensory scores and better chemical qualities, such as the content of gallocatechin (GC), gallocatechin gallate (GCG), free amino acids, solutable sugar, meanwhile the lightness decreased, the hue of tea brew color (b) increased, which meant the tea brew got darker and yellower. YAYTs roasted for 22 min also increased the contents of key odorants, such as benzaldehyde, nonanal, β-cyclocitral, linalool, nerol, α-cedrol, β-ionone, limonene, 2-methylfuran, indole, and longiborneol. Moreover, non-targeted metabolomics identified up to 14 differentially expressed metabolites through pair-wise comparisons, such as flavonoids, phenolic acids, sucrose, and critical metabolites, which were the main components corresponding to YAYT roasted for 22 min. In summary, the current results provide scientific guidance for the production of high quality YAYT.     

The Pharmacokinetics in Mice and Cell Uptake of Thymus Immunosuppressive Pentapeptide Using LC-MS/MS Analysis

Thymus immunosuppressive pentapeptide (TIPP) is a novel anti-inflammatory peptide with high efficacy and low toxicity. This study aims to establish a selective LC-MS/MS method for analyzing the analyte TIPP in biological samples, laying the foundation for further PK and PD studies of TIPP. Protein precipitation was conducted in acetonitrile supplemented with 2% formic acid and 25 mg/mL dithiothreitol as a stabilizer, which was followed by backwashing the organic phase using dichloromethane. The chromatographic separation of TIPP was achieved on a C18 column with a gradient elution method. During positive electrospray ionization, TIPP was analyzed via multiple-reaction monitoring. The linear relationships between the concentration of TIPP and peak area in murine plasma cell lysates, supernatants, and the final cell rinse PBS were established within the ranges of 20–5000 ng/mL, 1–200 ng/mL, 10–200 μg/mL, and 0.1–20 ng/mL, respectively (r² > 0.99). Validated according to U.S. FDA guidelines, the proposed method was proved to be acceptable. Such a method had been successfully applied to investigate the pharmacokinetics of TIPP in mice via subcutaneous injection. The plasma half-life in mice was 5.987 ± 1.824 min, suggesting that TIPP is swiftly eliminated in vivo. The amount of TIPP uptake by RBL-2H3 cells was determined using this method, which was also visually verified by confocal. Furthermore, the effective intracellular concentration of TIPP was deduced by comparing the intracellular concentration of TIPP and degrees of inflammation, enlightening further investigation on the intracellular target and mechanism of TIPP.     

Role of Natural Compounds and Target Enzymes in the Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurological condition. The rising prevalence of AD necessitates the rapid development of efficient therapy options. Despite substantial study, only a few medications are capable of delaying the disease. Several substances with pharmacological activity, derived from plants, have been shown to have positive benefits for the treatment of AD by targeting various enzymes, such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-secretase, γ-secretase, and monoamine oxidases (MAOs), which are discussed as potential targets. Medicinal plants have already contributed a number of lead molecules to medicine development, with many of them currently undergoing clinical trials. A variety of medicinal plants have been shown to diminish the degenerative symptoms associated with AD, either in their raw form or as isolated compounds. The aim of this review was to provide a brief summary of AD and its current therapies, followed by a discussion of the natural compounds examined as therapeutic agents and the processes underlying the positive effects, particularly the management of AD.