A new synthesis of 1,2,3,5‐tetrahydroimidazo[2,3‐b]‐[1,3]benzodiazocines

A new synthesis of 6‐carbomethoxy‐1,2,3,5‐tetrahydroirnidazo[2,3‐b][1,3]benzodiazocines 13 by the intramolecular cycloaddition reaction of methyl 2‐(1‐aziridinylmethyl)‐3‐(2‐ureidophenyl)propenoates 10 under Appel's dehydration conditions is described. The latter were readily obtained from 2‐nitrobenzalde‐hyde with methyl acrylate through the Baylis‐Hillman reaction.     

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.     

Human Serum Amyloid a Impaired Structural Stability of High-Density Lipoproteins (HDL) and Apolipoprotein (Apo) A-I and Exacerbated Glycation Susceptibility of ApoA-I and HDL

Human serum amyloid A (SAA) is an exchangeable apolipoprotein (apo) in high-density lipoprotein (HDL) that influences HDL quality and functionality, particularly in the acute phase of inflammation. On the other hand, the structural and functional correlations of HDL containing SAA and apoA-I have not been reported. The current study was designed to compare the change in HDL quality with increasing SAA content in the lipid-free and lipid-bound states in reconstituted HDL (rHDL). The expressed recombinant human SAA1 (13 kDa) was purified to at least 98% and characterized in the lipid-free and lipid-bound states with apoA-I. The dimyristoyl phosphatidylcholine (DMPC) binding ability of apoA-I was impaired severely by the addition of SAA, while SAA alone could not bind with DMPC. The recombinant human SAA1 was incorporated into the rHDL (molar ratio 95:5:1, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC): cholesterol: apoA-I) with various apoA-I:SAA molar ratios from 1:0 to 1:0.5, 1:1 and 1:2. With increasing SAA1 content, the rHDL particle size was reduced from 98 Å to 93 Å, and the α-helicity of apoA-I:SAA was decreased from 73% to 40% for (1:0) and (1:2), respectively. The wavelength maximum fluorescence (WMF) of tryptophan in rHDL was red-shifted from 339 nm to 345 nm for (1:0) and (1:2) of apoA-I:SAA, respectively, indicating that the addition of SAA to rHDL destabilized the secondary structure of apoA-I. Upon denaturation by urea treatment from 0 M to 8 M, SAA showed only a 3 nm red-shift in WMF, while apoA-I showed a 16 nm red-shift in WMF, indicating that SAA is resistant to denaturation and apoA-I had higher conformational flexibility than SAA. The glycation reaction of apoA-I in the presence of fructose was accelerated up to 1.8-fold by adding SAA in a dose-dependent manner than that of apoA-I alone. In conclusion, the incorporation of SAA in rHDL impaired the structural stability of apoA-I and exacerbated glycation of HDL and apoA-I.     

The Antioxidant and Hypolipidemic Effects of Mesona Chinensis Benth Extracts

In this study, the antioxidant and hypolipidemic effects of Mesona Chinensis Benth (MCB) extracts were evaluated. Seven fractions (F0, F10, F20, F30, F40, F50 and MTF) were obtained from the MCB ethanol extracts. Compared to the commercial antioxidants (vitamin C), MTF and F30 exhibited higher antioxidant activities in the antiradical activity test and the FRAP assay. The half-inhibition concentration (IC50) for MTF and F30 were 5.323 µg/mL and 5.278 µg/mL, respectively. MTF at 200 µg/mL significantly decreased the accumulation of TG in oleic acid (OA)-induced HepG2 cells and reversed the inhibitory effect of Compound C on AMPK (MTF and F30 significantly increased the glucose utilization of insulin-induced HepG2 cells). In addition, the components of MTF were identified by HPLC-MS, which were caffeic acid, quercetin 3-O-galactoside, isoquercetin, astragalin, rosmarinic acid, aromadendrin-3-O-rutinoside, rosmarinic acid-3-O-glucoside and kaempferol-7-O-glucoside. Through statistical correlations by Simca P software, it was found that the main antioxidant and hypolipidemic components of MCB might be caffeic acid, kaempferol-7-O-glucoside, rosmarinic acid-3-O-glucoside and aromadendrin-3-O-rutinoside, which may play important roles in the AMPK pathway. MTF and F30 in MCB could be potential health products for the treatment of hyperlipidemia.     

Facile Synthesis of Porous Ag Crystals as SERS Sensor for Detection of Five Methamphetamine Analogs

Porous noble metal nanomaterials have attracted extensive attention due to their high specific surface area and surface plasmon resonance effect. However, it is difficult to form porous structures due to the high mobility and low reduction potential of noble metal precursors. In this article, we developed a facile method for preparing porous Ag with a controllable structure at room temperature. Two kinds of Ag crystals with different porous structures were successfully prepared by using AgCl cubes as sacrificial templates. Through the galvanic replacement reaction of Zn and AgCl, Ag crystals with a sponge-like porous structure were successfully prepared. Additionally, using NaBH₄ as the reducing agent, we prepared granular porous Ag cubes by optimizing the amount of reducing agent. Both the sponge-like and granular porous Ag cubes have clean and accessible surfaces. In addition, we used the prepared two porous Ag cubes as substrate materials for SERS detection of five kinds of methamphetamine analogs. The experimental results show that the enhancement effect of granular porous Ag is better than that of sponge-like porous Ag. Furthermore, we probed the hot spot distribution of granular porous Ag by Raman mapping. By using granular porous Ag as the substrate material, we have achieved trace detection of 5 kinds of methamphetamine analogs including Ephedrine, Amphetamine, N-Methyl-1-(benzofuran-5-yl)propan-2-amine (5-MAPB), N-Methyl-1-(4-methoxyphenyl)propan-2-amine (PMMA) and N-Methyl-1-(4-fluorophenyl)propan-2-amine (4-FMA). Furthermore, to achieve qualitative differentiation of analogs with similar structures we performed density functional theoretical (DFT) calculations on the Raman spectra of the above analogs. The DFT calculations provided the vibrational frequencies, Raman activities, and normal mode assignment for each analog, enabling the qualitative differentiation of the above analogs.     

Development of a Quantitative Method for Detection of Multiclass Veterinary Drugs in Feed Using Modified QuPPe Extraction and LC–MS/MS

A method was developed for the rapid and quantitative analysis of 30 veterinary drugs belonging to 17 classes (amphenicols (1), anthelmintics (1), cephalosporins (4), coccidiostats (1), lincosamides (1), macrolide (1), nitroimidazole (1), penicillins (3), phenylhydrazines (1), polypeptides (1), pyrethrins (1), quinolones (5), sulfonamides (3), tetracycline (3), neuroleptic agents (1), triazene trypanocidal agents (1), other. (1)) in feeds. The proposed method with a modified Quick Polar Pesticides (QuPPe) sample preparation was validated for the determination of 30 veterinary drugs in feed samples by liquid chromatography triple-quadrupole mass spectrometry (LC–MS/MS). The sample was extracted with methanol containing 1% acetic acid and purified by dispersive solid-phase extraction (d-SPE) with C18. Good linearity (r² ≥ 0.98) was observed, and the LOQ values ranged from 10 to 200 µg/kg. Average recoveries ranged from 70.8 to 118.4%, and the relative standard deviation was ≤ 18.7%. This validated method was used in the determination of 30 veterinary drugs in 142 feed samples obtained from South Korea. The results show that lincomycin was present in only one of the tested feed samples, although it was detected at a value lower than the LOQ. In conclusion, this multi-residue method can be used for screening through the detection and quantitation of residual multiclass veterinary drugs in feed samples.     

The Influence of Tyrosol-Enriched Rhodiola sachalinensis Extracts Bioconverted by the Mycelium of Bovista plumbe on Scopolamine-Induced Cognitive,Behavioral, and Physiological Responses in Mice

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits, which are accompanied by memory loss and cognitive disruption. Rhodiola sachalinensis (RSE) is a medicinal plant that has been used in northeastern Asia for various pharmacological activities. We attempted to carry out the bioconversion of RSE (Bio-RSE) using the mycelium of Bovista plumbe to obtain tyrosol-enriched Bio-RSE. The objective of this study was to investigate the effects of Bio-RSE on the activation of the cholinergic system and the inhibition of oxidative stress in mice with scopolamine (Sco)-induced memory impairment. Sco (1 mg/kg body weight, i.p.) impaired the mice’s performance on the Y-maze test, passive avoidance test, and water maze test. However, the number of abnormal behaviors was reduced in the groups supplemented with Bio-RSE. Bio-RSE treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. Bio-RSE dramatically improved the cholinergic system by decreasing acetylcholinesterase activity and regulated oxidative stress by increasing antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)). The reduction in nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling in the brain tissue due to scopolamine was restored by the administration of Bio-RSE. Bio-RSE also significantly decreased amyloid-beta 1–42 (Aβ1–42) and amyloid precursor protein (APP) expression. Moreover, the increased malondialdehyde (MDA) level and low total antioxidant capacity in Sco-treated mouse brains were reversed by Bio-RSE, and an increase in Nrf2 and HO-1 was also observed. In conclusion, Bio-RSE protected against Sco-induced cognitive impairment by activating Nrf2/HO-1 signaling and may be developed as a potential beneficial material for AD.     

Faraday-Michelson system for quantum cryptography

Quantum key distribution provides unconditional security for communication. Unfortunately, current experimental schemes are not suitable for long-distance fiber transmission because of phase drift or Rayleigh backscattering. In this Letter we present a unidirectional intrinsically stable scheme that is based on Michelson-Faraday interferometers, in which ordinary mirrors are replaced with 90 degree Faraday mirrors. With the scheme, a demonstration setup was built and excellent stability of interference fringe visibility was achieved over a fiber length of 175 km. Through a 125 km long commercial communication fiber cable between Beijing and Tianjin, the key exchange was performed with a quantum bit-error rate of less than 6%, which is to our knowledge the longest reported quantum key distribution experiment under field conditions.