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The concise and highly convergent synthesis of the isodityrosine unit of seongsanamide A–D and its derivatives bearing a diaryl ether moiety is described. In this work, the synthetic strategy features palladium-catalyzed C(sp3)–H functionalization and a Cu/ligand-catalyzed coupling reaction. We report a practical protocol for the palladium-catalyzed mono-arylation of β-methyl C(sp3)–H of an alanine derivative bearing a 2-thiomethylaniline auxiliary. The reaction is compatible with a variety of functional groups, providing practical access to numerous β-aryl-α-amino acids; these acids can be converted into various tyrosine and dihydroxyphenylalanine (DOPA) derivatives. Then, a CuI/N,N-dimethylglycine-catalyzed arylation of the already synthesized DOPA derivatives with aryl iodides is described for the synthesis of isodityrosine derivatives.

The discovery and identification of effective components are pivotal in the research on Chinese medicinal prescriptions. Given two basic conditions for effective components in Chinese medicinal prescriptions, i.e., active structure and a certain level of drug exposure in the body(including the intestine), aquot;six-step strategyquot; for the effective compounds in Chinese medicinal prescriptions based on in vitro-in vivo integration(SSS for short) has been proposed and established, as well as the key technologies. SSS contains qualitative and quantitative analyses of components in five steps, including those in Chinese medicinal extract, intestinal contents, portal vein blood, liver, and peripheral blood. The components(prototype components and metabolites) with a certain exposure level(including in the intestine) and those with large differences between in vitro content and in vivo exposure or in exposure among various parts in the body are selected as the minority prioritized candidates. The sixth step is to screen the pharmacological activity of candidate components specifically extracted from Chinese medicinal materials or artificially synthesized. SSS can significantly narrow the screening range, enhance the hit rate, and speed up the identification of effective components specifically targeting indications. Based on the effective components identified by the SSS, thequot;upstreamquot; can be linked(mechanism research based on the effective components with clear structures) and thequot;downstreamquot; can be combined(development of innovative component-based Chinese medicine with definite pharmacodynamic composition). In this study, the concept of component-based Chinese medicine and specific applications of SSS in the development of component-based Chinese medicine are also introduced.

Inborn errors of metabolism (IEMs) can cause intellectual disability or even death in children. To evaluate the disease spectrum and genetic characteristics of IEMs in Jining City of Shandong Province in East China, we used tandem mass spectrometry (MS/MS) technology for IEMs screening combined with genetic analysis. Newborns were screened from July 14, 2014, to December 31, 2018. Amino acid and carnitine contents were detected by MS/MS. According to the results for normal newborns, the reference range of our laboratory was established with the percentile method. The suspected positive newborns were further diagnosed using next-generation sequencing. A total of 514,234 newborns were screened, and 265 were diagnosed with IEMs, with a detection rate of 1:1941. Of the 265 patients, 130 (49.06%) had organic acid disorders, 83 (31.32%) had amino acid disorders, 34 (12.83%) had fatty acid oxidation disorders, and 18 (6.79%) had urea circulatory disorders. PAHD and MMA were the two most common disorders. IEMs-associated genes were identified in 233 patients. Our data indicated that IEMs are never uncommon in Jining, and the disease spectrum and genetic background were clearly elucidated, contributing to the treatment and prenatal genetic counseling of these disorders in the region.

Highly crystalline NiOX usually requires high annealing temperature (>300 °C) which is incompatible with flexible substrate and might consume high amount of energy. Herein, we demonstrate a facile emulsion process to synthesize highly crystalline, low temperature deposition (

Background Mandatory newborn screening for metabolic disorders has not been implemented in most parts of China. Newborn mortality and morbidity could be markedly reduced by early diagnosis and treatment of inborn errors of metabolism (IEM). Methods of screening for IEM by tandem mass spectrometry (MS/MS) have been developed, and their advantages include rapid testing, high sensitivity, high specificity, high throughput, and low sample volume (a single dried blood spot). Methods Dried blood spots of 100,077 newborns obtained from Jining city in 2014-2015 were screened by MS/MS. The screening results were further confirmed by clinical symptoms and biochemical analysis in combination with the detection of neonatal deficiency in organic acid, amino acid, or fatty acid metabolism and DNA analysis. Results The percentages of males and females among the 100,077 infants were 54.1% and 45.9%, respectively. Cut-off values were established by utilizing the percentile method. The screening results showed that 98,764 newborns were healthy, and 56 out of the 1313 newborns with suspected IEM were ultimately diagnosed with IEM. Among these 56 newborns, 19 (1:5267) had amino acid metabolism disorders, 26 (1:3849) had organic acid metabolism disorders, and 11 (1:9098) had fatty acid oxidation disorders. In addition, 54 patients with IEM were found to carry mutations, and the other 2 patients had argininemia. Conclusions Fifty-six cases of metabolic disorders in Jining were confirmed via newborn screening (NBS) by MS/MS. Early diagnosis and treatment are crucial for the survival and well-being of affected children. A nationwide NBS program using MS/MS is recommended, especially in poor areas of China.

To characterize of the constituents in rat urine after oral administration of Radix Astragali decoction, a HPLC-DAD-MS/MS technique had been developed. Urine collected from 0 to 24 h, after administration, was purified using a C18 solid-phase extraction cartridge, and then detected by an on-line MS/MS detector. By comparing the retention times and MS/MS data with those obtained from authentic compounds and the published data, a total of 11 compounds including six flavonoids, one dipeptide, one triterpenoid and three of their metabolites in urine were identified. Compounds daidzein, genistein, quercetin, L-asparamide-D-phenylalanine, 4,2′,4′-trihydroxychalcone, Astragaloside-IV, daidzein sulfate, and kaempferol sulfate were for the first time detected by HPLC-MS/MS technique in urine. The present research results success-fully narrowed the range of effective constituents to be found in Astragalus membranaceus and would be useful for the following action mechanism research of this traditional Chinese medicine in treating various diseases.

The solubility of silybin in aqueous hydrochloric acid solution has been measured at temperatures range from 293.15 to 313.15 K. Experimental result shows that the solubility increase with the increase of both temperature and pH value. The solubility data was analyzed by a general salt-effect rule and a hydration–ionization model. We have found that the salt-effect rule is obeyed for pH 3 where the concentration of hydrogen ion is very low. The break down of salt-effect rule has been explained by employing a model of molecular hydration–ionization where quantum chemical calculation was performed to support this model by optimizing the geometries of silybin–water complex. Based on this model, the break down of the salt-effect rule is caused by that silybin's acidity increases with the increase of the pH value, which leads to the increase of the solubility at the higher pH regime. The predicted pKa also agrees well with the experimental result.

Feitai, a Chinese medicine formulation, has been shown to protect against lung fibrosis induced by bleomycin (BLM). In the present study, we investigated the effect of Feitai on transforming growth factor (TGF)-beta1 and monocyte chemoattractant protein-1 (MCP-1), which play important roles in the pathogenesis of BLM-induced lung fibrosis. The results demonstrated that Feitai could significantly attenuate BLM-induced acute lung inflammation and subsequent lung fibrosis. Meanwhile, the expression of MCP-1 and TGF-beta1 mRNA in the lungs increased in the BLM-treated group compared with the saline-instilled control group and Feitai treatment significantly decreased cytokine expression in BLM-treated mice. In addition, Feitai diminished the accumulation of MCP-1- and TGF-beta1-positive cells in lung tissues at the time of peak mRNA levels. In summary, the results of the present study indicate that treatment with Feitai ameliorates BLM-induced lung fibrosis, at least in part via the inhibition of MCP-1 and TGF-beta1 expression.

Viscosity and density data for the ternary solution of hexanedioic acid + polyvinylpyrrolidone (PVP k30) + water at temperatures 298.15, 303.15, 308.15 and 313.15 K have been measured. On the basis of the Eyring and Feakins equation, the viscosity B-coefficients and the activation parameters for viscous flow of the solution have been evaluated. The effect of temperature and PVP concentration on these parameters has been discussed. With the increase in PVP concentration, the activation free energy of diffusion for hexanedioic acid is decreased. This is an indication that the diffusion ability of hexanedoic acid is improved by the addition of PVP into solution.

Viscosity and density data for the system of hexanedioic acid dissolved in poly(ethylene glycol) 6000 (PEG6000) + water solvents at 298.15, 303.15, 308.15 and 313.15 K have been determined. The viscosity B-coefficients and partial molar volumes for hexanedioic acid in PEG aqueous solutions have been calculated. The effect of temperature and PEGs concentration on the B-coefficients are discussed on the basis of the Feakins equation. The contribution of solute and mixed solvents to the activation parameters, (Δμ3≠, ΔH3≠, ΔS3≠, ΔG120≠, ΔH120≠ and ΔS120≠), for viscous flow of the solution have been evaluated, together with the Gibb’s energy of transfer for the solute from the ground state solvent to the hypothetical viscous transition state solvent (ΔG3≠(1−1′)).

Two novel steroidal saponins (timosaponin BIII-a, timosaponin BIII-b) together with a known steroidal saponin (timosaponin BII-b) were prepared by the dilute acid hydrolysis of timosaponin BIII. Their structures were elucidated by means of 1D, 2D NMR and TOF-MS spectral analysis.

To determine the impact of expanded newborn screening using tandem mass spectrometry (MS/MS) on the overall detection rate of inborn errors of metabolism in Zhejiang province and to assess the outcome of the patients who were diagnosed.Blood spots were collected between days 3 and 6 of life from the newborns. All samples were subjected to MS/MS analysis using Waters Quattro API. Confirmation tests included amino acid analysis, urinary organic acids by GC-MS, routine blood analysis, biochemistry, blood gas analysis, blood glucose and ammonia tests, blood homocysteine, lactate and pyruvate tests, urine acetone tests, biotin and biotin enzyme profile and DNA analysis. Standard treatment protocol was given to the patients. Protein restricted diet, special powdered formula and medicines recommended for the patients with amino acidemias. Protein restricted diet and L-carnitine, folic acid and Vitamin B12 supplementation were given for the patients with organic acidemia. L-carnitine was given to the patients with primary carnitine deficiency. The overall epidemiology, prognosis, follow-up of the screening program were also investigated in the neonates.A total of 129 415 neonates were investigated for 26 inborn errors of metabolism during the period. Twenty-three newborns were confirmed as having inborn errors of metabolism, including 13 with amino acidemias, 6 with organic acidemias and 4 with fatty acid oxidation disorders. The prevalence was 1:5626. Positive predictive value was 2.10%, specificity was 99.72% and sensitivity 100%. Seventeen children remain asymptomatic during the follow-up. Five patients had motor and mental developmental delay. One patient presented metabolic disorders during the follow-up. No death occurred in this series of patients.This strategy represents a valuable preventive medicine approach by enabling diagnosis and treatment before the onset of symptoms.

In the present study, the anti-diabetic effects of a traditional Chinese medicinal formula extract, TongGuanWan, were investigated in type 2 diabetic animals. It was orally administered to C57BL/KsJ-db/db mice once a day for 4 weeks at the doses of 62, 125, and 250 mg/kg body weight. TongGuanWan significantly lowered the blood glucose and glycosylated haemoglobin levels as well as improved the glucose tolerance in db/db mice. The serum triglyceride levels in the db/db mice were significantly decreased, whereas the high-density lipoprotein cholesterol levels were significantly increased, after treatment with this herbal formula. TongGuanWan also markedly decreased the animals' body weights compared to those of the control db/db group but did not alter food intake. The effects of TongGuanWan were compared to those of the drug rosiglitazone. In addition, five main constituents of TongGuanWan, mangiferin, berberine, cinnamic aldehyde, timosaponin BII, and timosaponin AIII, were quantified using high performance liquid chromatography coupled with a diode array and an evaporative light scattering detector (HPLC-DAD-ELSD). These results suggest that TongGuanWan may be useful for the treatment of type 2 diabetes.

A new cadinane-type sesquiterpenoid, tatarinowin A (1), two phenylpropanoids, tatarinoids A (2) and B (3), and a trinorlignan, tatarinoid C (4), along with 15 known compounds including two pairs of mixtures were isolated from the rhizome of Acorus tatarinowii. The absolute configurations of 1-4 were established by computation of specific rotation values. The isolated compounds were evaluated for their cAMP regulatory activity by the AlphaScreen assay.

Two new iridoid diastereoisomers (1, 2), together with five known compounds, were isolated from the flowers of Plumerian rubra L. cv. acutifolia. Their structures were elucidated by the means of in-depth spectroscopic and mass-spectrometric analyses, particularly 1D and 2D NMR spectroscopy.

To study the polysaccharide of Condonopsis pilosula.The polysaccharide, CPP-1, was purified by DE-52 cellulose and Sephadex G-200 gel column chromatography. Purity and molecular weight of the polysaccharide were determined by gel permeation chromatography. Methylation analysis, periodate oxidation and degradation, IR, 1H-NMR and 13C-NMR methods were adopted to elucidate the chemical structure.The molecular weight of CPP-1 was estimated to be 7.5 x 10(4), and the structure of CPP-1 was a beta-(2 --1) linked beta-D-fructosan.CPP-1 was a neutral homosaccharide.

Silybin is a main component in silymarin, which is an antihepatotoxic polyphenolic substance isolated from the milk thistle plant, Silybum marianum . A major problem in the development of an oral solid dosage form of this drug is the extremely poor aqueous solubility. In present work, the solubility of silybin in aqueous poly(ethylene glycol) 6000 (PEG 6000) solution at the temperature range from 293.15 to 313.15 K was measured by a solid liquid equilibrium method. The aim of this study is to investigate the possible effect of poly(ethylene glycol) concentration and temperature on the solubility of the drug, and to reveal the solubilization capacity of the polymer for the drug. Experimental results reveal that the solubility of silybin increases with the increase both in PEG's concentration and temperature. With the increase in PEG's concentration, the transfer enthalpy and entropy for silybin from water to aqueous PEG solution increases first in a positive region, and then decreases to a negative region. The transfer enthalpy is lower than the entropy term. A modified Universal Quasi Chemical (UNIQUAC) model was used to correlate solubility data.