Chips and Qi: microcomponent-based analysis in traditional Chinese medicine

Over the last 50 years or so Traditional Chinese medicine (TCM) has been subject to intensive basic and clinical research. Although the effectiveness and remarkable safety of TCM have been documented after controlled clinical studies, there are several herbal and animal parts that are toxic or difficult to identify. DNA polymorphism-based assays have recently been developed for the identification of herbal medicines. In this approach, small amounts of DNA are amplified by the polymerase chain reaction and the reactions products are analyzed by gel electrophoresis, sequencing, or hybridization with species-specific probes. With the DNA based identification of TCM materials as an example, chip-based analytical micro devices were developed with the goal of fabricating an integrated device that will enable sample preparation, amplification, and analysis on a single microchip-based device ("lab-on-a-chip"). The application of a silicon-based polymerase chain reaction microreactor and a DNA microarray for the DNA sequence-based identification of toxic medicinal plants is reported here.     

Phototitrimetric determination of sulfhydryl compounds witho-hydroxymercuribenzoic acid using dithiofluorescein as an indicator

Summary A phototitrimetric method for the determination of sulfhydryl compounds in an aqueous medium is described.o-Hydroxymercuribenzoic acid is used as a titrant with dithiofluorescein as an indicator. Disulfide amino acids like cystine and-substituted DL-cystines are reduced with sodium borohydride before titration. All amino acids were determined to the limit of 1.0mol with an error of less than 4%. A selective phototitrimetric method for the determination of-mercaptopyruvate in presence of cysteine and glutathione is described. This method can be extended to the microdetermination of other similar sulfhydryl compounds in biological materials.

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Zusammenfassung Eine phototitrimetrische Bestimmungsmethode für Sulfhydrylverbindungen in wäßriger Phase wurde beschrieben. Als Maßflüssigkeit diento-Hydroxymercuribenzoesäure, als Indikator Dithiofluorescein. Aminosäuredisulfide wie Cystin und-substituierte DL-Cystine werden vor der Titration mit Natriumborhydrid reduziert. Alle Aminosäuren lassen sich bis zur Größenordnung von 1,0Mol mit einem Fehler von weniger als 4% bestimmen. Eine selektive phototitrimetrische Bestimmung von-Merkaptopyruvat in Gegenwart von Cystein und Glutathion wurde angegeben. Das Verfahren läßt sich auch für andere Sulfhydrylverbindungen in biologischem Material anwenden.

     

Orally administered bismuth drug together with N-acetyl cysteine as a broad-spectrum anti-coronavirus cocktail therapy

The emergence of SARS-CoV-2 variants of concern compromises vaccine efficacy and emphasizes the need for further development of anti-SARS-CoV-2 therapeutics, in particular orally administered take-home therapies. Cocktail therapy has shown great promise in the treatment of viral infection. Herein, we reported the potent preclinical anti-SARS-CoV-2 efficacy of a cocktail therapy consisting of clinically used drugs, e.g. colloidal bismuth subcitrate (CBS) or bismuth subsalicylate (BSS), and N-acetyl-l-cysteine (NAC). Oral administration of the cocktail reduced viral loads in the lung and ameliorated virus-induced pneumonia in a hamster infection model. The mechanistic studies showed that NAC prevented the hydrolysis of bismuth drugs at gastric pH via the formation of the stable component [Bi(NAC)₃], and optimized the pharmacokinetics profile of CBS in vivo. Combination of bismuth drugs with NAC suppressed the replication of a panel of medically important coronaviruses including Middle East respiratory syndrome-related coronavirus (MERS-CoV), Human coronavirus 229E (HCoV-229E) and SARS-CoV-2 Alpha variant (B.1.1.7) with broad-spectrum inhibitory activities towards key viral cysteine enzymes/proteases including papain-like protease (PL^pro), main protease (M^pro), helicase (Hel) and angiotensin-converting enzyme 2 (ACE2). Importantly, our study offered a potential at-home treatment for combating SARS-CoV-2 and future coronavirus infections.

A cocktail therapy comprising bismuth drugs and N-acetyl-l-cysteine is reported to suppress the replication of SARS-CoV-2 via the oral route. The broad-spectrum inhibitory activities of the combination upon key viral cysteine enzymes are verified.     

A multiple regression model for urban traffic noise in Hong Kong

This article describes the roadside traffic noise surveys conducted in heavily built-up urban areas in Hong Kong. Noise measurements were carried out along 18 major roads in 1999. The measurement data included L10, L50, L90, Leq, Lmax, the number of light vehicles, the number of heavy vehicles, the total traffic flow, and the average speed of vehicles. Statistical analysis using the analysis of variance (ANOVA) and Tukey test (p<0.05) reveals that the total traffic flow and the number of heavy vehicles are the most significant factors of urban traffic noise. Multiple regression was used to derive a set of empirical formulas for predicting L10 noise level due to road traffic. The accuracy of these empirical formulas is quantified and compared to that of another widely used prediction model in Hong Kong--the Calculation of Road Traffic Noise. The applicability of the selected multiple regression model is validated by the noise measurements performed in the winter of 2000.     

Local convergence of quasi-Newton methods for B-differentiable equations

We study local convergence of quasi-Newton methods for solving systems of nonlinear equations defined by B-differentiable functions. We extend the classical linear and superlinear convergence results for general quasi-Newton methods as well as for Broyden's method. We also show how Broyden's method may be applied to nonlinear complementarity problems and illustrate its computational performance on two small examples.     

Highly trans‐Selective Arylation of Achmatowicz Rearrangement Products by Reductive γ‐Deoxygenation and Heck–Matsuda Reaction: Asymmetric Total Synthesis of (−)‐Musellarins A–C and Their Analogues

Fully functionalized pyranuloses derived from Achmatowicz rearrangement (AR) are versatile building blocks in organic synthesis. However, access to trans‐2,6‐dihydropyrans from pyranuloses remains underexplored. Herein, we report a new two‐step trans arylation of AR products to access 2,6‐trans‐dihydropyranones. This new trans‐arylation method built on numerous plausible, but unsuccessful, direct arylation reactions, including Ferrier‐type and Tsuji–Trost‐type reactions, was finally enabled by an unprecedented, highly regioselective γ‐deoxygenation of AR products by using Zn/HOAc and a diastereoselective Heck–Matsuda coupling. The synthetic utility of the reaction was demonstrated in the first asymmetric total synthesis of (?)‐musellarins A–C and 12 analogues in 11–12 steps. The brevity and efficiency of our synthetic route permitted preparation of enantiomerically pure musellarins and analogues (>20 mg) for preliminary cytotoxicity evaluation, which led us to identify two analogues with three‐to‐six times greater potency than the musellarins as promising new leads.     

A new carotenoid glycoside from Rehmannia glutinosa

A new carotenoid glycoside, namely neo-rehmannioside (1), together with five known compounds, 6-O-seco-hydroxyaeginetoyl ajugol (2), oxyrehmaionoside B (3), ajugol (4), geniposidic acid (5) and geniposide (6) was isolated from the 95% ethanol extract of dry roots of Rehmannia glutinosa. The structure of the new compound (1) was determined based on MS, IR, 1-D and 2-D NMR spectral data.