Construction of central and axial chirality via Pd(II)/Bim-catalyzed asymmetric dearomative Michael reaction of polycyclic tropones.

A highly enantioselective Pd/Bim-catalyzed dearomative Michael reaction applying polycyclic tropones as non-benzenoid aromatic Michael acceptors and arylboronic acids as aryl pronucleophiles has been developed. The bridged biaryls bearing central and axial chirality, including pentacyclic cyclohepta[b]indoles and 6,7-dihydrodibenzo[a,c][7]annulen-5-ones, are generally generated in good to high yields and excellent enantioselectivities and can be readily transformed into useful derivatives.

Establishment of a multicomponent quality control method and the transfer characteristics of five markers from Qidongning Formula to rat tissues by HPLC-QQQ-MS/MS.

Introduction: Traditional Chinese medicine compound preparations have become an increasingly utilized strategy for tumour treatment. Qidongning Formula (QDN) is a kind of antitumour compound preparation used in hospitals, and it can inhibit the growth of lung cancer cells. However, due to the complexity of botanical drugs, the quality evaluation of QDN is inconsistent, affecting clinical efficacy and posing potential safety risks for clinical application. Additionally, tissue distribution is an integral part of the drug development process. Methods: To study the distribution characteristics of markers in compound preparations and rat tissues, a novel HPLC-QQQ-MS/MS quantitative analytical method was established to determine five markers in QDN simultaneously, and the method was verified. Results and discussion: The analytical results showed that the contents of salidroside (51.6 ± 5.75 µg/g), calycosin-7-O-ß-D-glucoside (94.2 ± 15.4 µg/g), specnuezhenide (371 ± 72.5 µg/g), formononetin (23.8 ± 5.39 µg/g), and polyphyllin I (87.7 ± 10.6 µg/g) were stable in different batches of QDN. After intragastric administration (13.5 g/kg) in rats for 1 h, four markers in the QDN, except polyphyllin I, were distributed in most tissues. QDN was distributed chiefly in the stomach and small intestine, followed by the liver or kidney. The study also found that specnuezhenide had the highest concentration in both QDN and rat tissues (102 ± 22.1 µg/g in the stomach), while formononetin had the highest transfer rate (0.351%) from QDN to rat intestines. The above research lays a quality research foundation for the antitumour application of QDN and provides a scientific reference for the quality control of Chinese medicine compound preparations.

[Identification of ecological functional zoning and its influencing factors in the Sihu Lake Basin, China]. / å››æ¹–æµåŸŸç”Ÿæ€åŠŸèƒ½åˆ†åŒºåŠå ¶å½±å“å› ç´ è¯†åˆ«.

Rational delineation of ecological functional areas and clarification of their driving factors are of significance for maintaining regional ecosystem stability. We assessed six ecosystem services of Sihu Lake Basin located in Jianghan Plain using InVEST and RUSLE models and recreational scoring methods. By using K-means clustering, we identified the ecosystem service bundles, and delineated the ecological functional areas in combination with ecological sensitivity and ecosystem service bundles. The dominant driving factors of different ecological functional areas were analyzed by Geodetector. The results showed that the spatial distributions of habitat quality and carbon sequestration services were similar, with high values being mainly concentrated in Changhu Lake Basin and Honghu Lake Basin. However, the spatial distributions of crop production and soil conservation services were different, with high-value areas concentrated in the northwest area with mountains. The high values of water production service were mainly concentrated in the eastern part of Honghu Lake Basin, while the high-value areas of ecological recreation service were mainly concentrated in the northwest area and the southern part of Honghu Lake Basin. The Sihu Lake Basin could be classified into crop production bundle, habitat quality bundle, and urban living bundle according to cluster analysis. The low ecological sensitivity areas accounted for 59.0% of the Sihu Lake Basin. We classified the study area into ecological restoration areas, ecological conservation areas, ecological transition areas, ecological development areas, and comprehensive use areas by combination of ecological sensitivity and ecosystem service bundles. The geodetector results indicated that the driving factors of each ecological function zone were significantly different. The natural factors significantly influenced the ecological restoration zone, while the normalized vegetation index and population density were the main influencing factors in the ecological conservation zone and the ecological development zone, respectively. Land use type was the main influencing factor in the ecological transition zone and the comprehensive use zone. The results could provide important support for coordinated regional social development and environmental protection.

Simultaneous determination of twenty-nine active compounds in fuzhengjiedu granules by HPLC-QQQ-MS/MS.

As an empirical medicine of traditional Chinese medicine, Fuzhengjiedu Granules have shown an effect against COVID-19 in clinical and inflammatory animal models. It is formulated with eight herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Glycyrrhizae Radix Et Rhizoma, Lonicerae Japonicae Flos, Gleditsiae Spina, Fici Radix, Pogostemonis Herba, and Citri Reticulatae Pericarpium. This study established a high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS) method by simultaneously determining 29 active compounds in the granules with significant content differences. Separation by gradient elution using acetonitrile and water (0.1% formic acid) as mobile phases was performed on a Waters Acquilty UPLC T3 column (2.1 mm × 100 mm, 1.7 µm). A triple quadrupole mass spectrometer, operating in positive and negative ionization modes, was used for multiple reaction monitoring to detect the 29 compounds. All calibration curves showed good linear regression (r2 > 0.998). RSDs of precision, reproducibility, and stability of active compounds were all lower than 5.0%. The recovery rates were 95.4-104.9%, with RSDs< 5.0%. This method was successfully used to analyze the samples, and the results showed that 26 representative active components from 8 herbs were detected in the granules. While aconitine, mesaconitine, and hypaconitine were not detected, indicating that the existing samples were safe. The granules had the maximum and minimum content of hesperidin (27.3 ± 0.375 mg/g) and benzoylaconine (38.2 ± 0.759 ng/g). To conclude, a fast, accurate, sensitive, and reliable HPLC-QQQ-MS/MS method was established, which can simultaneously detect 29 active compounds that have a considerable difference in the content of Fuzhengjiedu Granules. This study can be used to control the quality and safety of Fuzhengjiedu Granules and provide a basis and guarantee for further experimental research and clinical application.

Ground-state intramolecular proton transfer inhibits the selective methylation on quinoline and pyridine derivatives.

Methylation is one of the crucial steps for drug discovery, organic synthesis, and catalysis. Despite being a versatile and well-known chemical reaction, its chemoselectivity has not been well addressed. In this paper, we reported a thorough experimental and computational investigation of the selective N-methylation of N-heterocyclic compounds, mainly quinolines and pyridines. These reactions were conducted in a base-free manner under ambient conditions using iodomethane as the methylating reagent, exhibited good chemoselectivity, and were tolerant of other amine, carboxyl, or hydroxyl functional groups without needing protection. To this end, 13 compounds were synthesized as a proof-of-concept and 7 crystal structures were obtained. However, the chemoselectivity failed in the presence of a thiol group. Detailed quantum chemical calculations provided insights into the N-methylation mechanism and its selectivity and demonstrated that the isomerization induced by ground-state intramolecular proton transfer (GSIPT) in the presence of a thiol group inhibits the N-methylation.

Dietary approach to stop hypertension diet and risk of coronary artery disease: a meta-analysis of prospective cohort studies.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet can lower blood pressure, but its role in preventing coronary artery disease (CAD) remains in debate. Thus, we performed a meta-analysis of prospective cohort studies to address this issue. We carried out a systematical search in databases of PubMed and Embase to screen out eligible publications. Relative risks (RRs) of CAD in the included studies were summarised using random-effect meta-analysis. Dose-response association between DASH diet score and CAD risk was also evaluated. Seven prospective studies were finally included, with a total of 377,725 participants and 15,074 CAD cases. Compared to lower adherence, higher adherence to the DASH diet was associated a decreased risk of CAD (RR 0.82, 95% confidence interval [CI]: 0.78-0.87). Subgroup and sensitivity analyses supported the preventive effects of DASH diet against CAD, and there was no indication of publication bias. For a curvilinear dose-response pattern, the RRs (95% CIs) of CAD for the 4 knots (5th, 35th, 65th and 95th percentiles) of DASH diet score were 0.93 (0.89-0.98), 0.87 (0.80-0.95), 0.81 (0.72-0.90) and 0.74 (0.68-0.82), respectively. For a linear dose-response manner, each 4-point increase in the DASH diet score could reduce the risk of CAD by 5% (RR 0.95, 95% CI: 0.94-0.97). The results of our study indicate that higher adherence to the DASH diet confers a reduced risk of developing CAD.

[Correlation of Heart Rate and Geographical Environmental Factors with Reference Values of Left Ventricular Ejection Fraction in Healthy Adult Males].

Objective To establish a model for obtaining the reference values of left ventricular ejection fraction(LVEF) in Chinese healthy adult males by exploring the relationships of these reference values with heart rate and geographical environment factors. Methods LVEF and heart rate reference values (X1) were collected from 3502 healthy adult males from 2006 to 2016. Correlation analysis and ridge regression were employed to extract dependent geographical environment factors and predict the LVEF reference values. The Kriging interpolation was applied to reveal the spatial distribution of the LVEF reference values. Results LVEF and heart rate (X1) were significantly correlated with five geographical environment factors. LVEF was negatively correlated with heart rate (X1),latitude (X3),and annual range of temperature (X9) and positively correlated with annual mean air temperature (X6),annual mean relative humidity (X7),and annual precipitation amount (X8). The reference values of LVEF had a negative correlation with heart rate. The ridge regression equation of LVEF reference values and geographical environment factors was as follows:Y=68.464-0.0949X3-0.0619X6-0.00128X7+0.00069X8-0.0199X9±3.329. The equation of LVEF reference values with heart rate and geographical environment factors was Y=75.923-0.1035X1-0.0958X3-0.0741X6+0.00094X7+0.00081X8-0.0211X9±3.288. Conclusion The LVEF reference values among Chinese healthy adult males decreased from south to north. They can be determined based on the regression models after the geographical factors of a certain region are obtained. The new model offers a geographic basis for the establishment of LVEF reference values.