Progress towards the Total Syntheses of Amaryllidaceae Alkaloids γ-Lycorane.

γ-Lycorane, a degradation product of the Aromaticaceae alkaloid lycorine, is one of the most attractive molecules in the Aromaticaceae family. It remains a popular target for synthesis due to its pentacyclic structure, which presents a vehicle for demonstrating the utility of new synthetic strategies. Various synthetic methods have been developed by synthetic chemists since the first synthesis of γ-lycorane by Nasuo in 1966. Thus, this review presents an overview of the literature on the ways utilized within the synthesis of γ-lycorane in racemic and enantiopure forms via electrophilic arylation, Pd-catalyzed C-C coupling, Bischler-Napieralski cyclization, Pictet-Spengler cyclization, photocyclization, radical cyclization, chiral pool synthesis, chiral auxiliary-mediated synthesis, and catalytic asymmetric synthesis, ranging from 1966 to 2022.

Tumor length-to-height ratio as a predictor of recurrent laryngeal nerve lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma.

BACKGROUND: The metastasis of laryngeal nerve lymph node is mostly found in the upper-and middle esophageal cancer, the ratio of esophageal length from the upper incisors to the position where the esophageal tumor began to appear as proven via endoscopy to the height (LH) is likely to affect the possibility of detection of recurrent laryngeal nerve(RLN) lymph node (LN) metastasis. The purpose of this study was to evaluate the predictive value of LH for RLN LN metastasis. METHODS: One hundred and eighty-eight patients (mean age: 64.89 years; range: 46-84 years) calculated LH before esophagectomy and LN dissection were retrospective analyzed. The clinicopathological data of the patients, LH calculations were compared with the RLN LN histopathologic results to investigate the effect of LH on the diagnosis of RLN LN metastasis. RESULTS: The LH correlated with that of the RLN LN metastasis in receiver-operating-characteristic (ROC) analysis. Our ROC analyses demonstrated the optimal cut-off value was 16.66 for LH with an area under the curve value of 0.69. Compared with the Height (H) and L, ROC curve for LH have better performance in predicting the RLN LN metastasis. CONCLUSIONS: LH is a useful predictive tool in the evaluation of RLN LN metastasis for esophageal cancer. The present findings support the result that LH can be an indicator of RLN LN dissection.

XRCC1 genetic polymorphism acts a potential biomarker for lung cancer.

Lung cancer is one of the most common but serious cancers in the world. Both the X-ray repair cross-complementing group 1 (XRCC1) gene and the human multidrug resistance 1 (MDR1) gene are important candidate genes influencing the susceptibility to various diseases, including lung cancer. This study aimed to assess the correlation of genetic polymorphisms in XRCC1 and MDR1 with the susceptibility to lung cancer. In this study, a total of 320 lung cancer patients and 346 cancer-free controls in Chinese population were enrolled in this study. Data about the clinical characteristics and related risk factors of lung cancer were collected by questionnaires. The single-nucleotide polymorphisms (SNPs) of XRCC1 and MDR1 genes were genotyped by created restriction site-polymerase chain reaction method. Our data showed that the risk for lung cancer increased significantly among the variant Arg194Trp (C > T, rs1799782) and Arg399Gln (G > A, rs25487) of XRCC1, but there are no significant differences in the allelic and genotypic frequencies of c.1564A > T and c.3073A > C of MDR1 between lung cancer patients and cancer-free controls. In conclusion, these preliminary results suggest that the C > T, rs1799782 and C > T, rs25487 of XRCC1 genetic variants might be used as molecular markers for detecting lung cancer susceptibility.

Large-scale prediction of human kinase-inhibitor interactions using protein sequences and molecular topological structures.

The kinase family is one of the largest target families in the human genome. The family's key function in signal transduction for all organisms makes it a very attractive target class for the therapeutic interventions in many diseases states such as cancer, diabetes, inflammation and arthritis. A first step toward accelerating kinase drug discovery process is to fast identify whether a chemical and a kinase interact or not. Experimentally, these interactions can be identified by in vitro binding assay - an expensive and laborious procedure that is not applicable on a large scale. Therefore, there is an urgent need to develop statistically efficient approaches for identifying kinase-inhibitor interactions. For the first time, the quantitative binding affinities of kinase-inhibitor pairs are differentiated as a measurement to define if an inhibitor interacts with a kinase, and then a chemogenomics framework using an unbiased set of general integrated features (drug descriptors and protein descriptors) and random forest (RF) is employed to construct a predictive model which can accurately classify kinase-inhibitor pairs. Our results show that RF with integrated features gave prediction accuracy of 93.76%, sensitivity of 92.26%, and specificity of 95.27%, respectively. The results are superior to those by only considering two separated spaces (chemical space and protein space), demonstrating that these integrated features contribute cooperatively. Based on the constructed model, we provided a high confidence list of drug-target associations for subsequent experimental investigation guidance at a low false discovery rate.

Genome-scale screening of drug-target associations relevant to Ki using a chemogenomics approach.

The identification of interactions between drugs and target proteins plays a key role in genomic drug discovery. In the present study, the quantitative binding affinities of drug-target pairs are differentiated as a measurement to define whether a drug interacts with a protein or not, and then a chemogenomics framework using an unbiased set of general integrated features and random forest (RF) is employed to construct a predictive model which can accurately classify drug-target pairs. The predictability of the model is further investigated and validated by several independent validation sets. The built model is used to predict drug-target associations, some of which were confirmed by comparing experimental data from public biological resources. A drug-target interaction network with high confidence drug-target pairs was also reconstructed. This network provides further insight for the action of drugs and targets. Finally, a web-based server called PreDPI-Ki was developed to predict drug-target interactions for drug discovery. In addition to providing a high-confidence list of drug-target associations for subsequent experimental investigation guidance, these results also contribute to the understanding of drug-target interactions. We can also see that quantitative information of drug-target associations could greatly promote the development of more accurate models. The PreDPI-Ki server is freely available via: http://sdd.whu.edu.cn/dpiki.

[Distribution characteristics and risk factors of carotid atherosclerosis in middle-aged and elderly Chinese].

OBJECTIVE: To describe the distribution characteristics of carotid atherosclerosis and to analyze its association with cardiovascular risk factors in middle-aged and elderly Chinese. METHODS: In 2007, the second cross-sectional examination for cardiovascular risk factors and B-mode ultrasound imaging on carotid arteries were performed in a Chinese population consisting of 2681 subjects aged 43-81 years old from two cohorts participants of the People's Republic of China/United States of America collaborative study (USA-PRC study) and the Chinese multi-provincial cohort study (CMCS). The association of cardiovascular risk factors with intima-media thickening (ITM) and plaque of carotid arteries was analyzed. RESULTS: (1) The mean intima-media thickening (Mean-IMT) of carotid artery was 0.68 mm, the maximal intima-media thickening (Max-IMT) was 1.07 mm. (2) The prevalence rate of carotid plaque was 60.3% in all subjects. As for the different sites of carotid arteries, the plaque prevalence rate at carotid bulb was 61.2% for male and 51.6% for female (chi2 = 23.44, P < 0.01), and at the internal carotid artery was 24.7% for male and 12.2% for female (chi2 = 69.57, P < 0.01), at the common carotid artery was 20.9% for male and 13.8% for female (chi2 = 23.18, P < 0.01). (3) After adjusting for age and other cardiovascular risk factors, the Mean-IMT and Max-IMT increased with elevated levels of systolic blood pressure, plasma glucose and low density lipoproteins cholesterol (LDL-C) (all P < 0.05). Hypertension, diabetes, smoking and high LDL-C (P < 0.05) were independent predict factors for the risk of carotid plaque. CONCLUSION: The carotid atherosclerosis was common in middle and older age Chinese and was positively associated with classical cardiovascular disease risk factors.

[The NIR spectra based variety discrimination for single soybean seed].

With the development of soybean producing and processing, the quality breeding becomes more and more important for soybean breeders. Traditional sampling detection methods for soybean quality need to destroy the seed, and does not satisfy the requirement of earlier generation materials sieving for breeding. Near infrared (NIR) spectroscopy has been widely used for soybean quality detection. However, all these applications were referred to mass samples, and they were not suitable for little or single seed detection in breeding procedure. In the present study, the acousto--optic tunable filter (AOTF) NIR spectroscopy was used to measure the single soybean seed. Two varieties of soybean were measured, which contained 60 KENJIANDOU43 seeds and 60 ZHONGHUANG13 seeds. The results showed that NIR spectra combined with soft independent modeling of class analogy (SIMCA) could accurately discriminate the soybean varieties. The classification accuracy for KENJIANDOU43 seeds and ZHONGHUANG13 was 100%. The spectra of single soybean seed were measured at different positions, and it showed that the seed shape has significant influence on the measurement of spectra, therefore, the key point for single seed measurement was how to accurately acquire the spectra and keep their representativeness. The spectra for soybeans with glossy surface had high repeatability, while the spectra of seeds with external defects had significant difference for several measurements. For the fast sieving of earlier generation materials in breeding, one could firstly eliminate the seeds with external defects, then apply NIR spectra for internal quality detection, and in this way the influence of seed shape and external defects could be reduced.

[Prediction value of blood lipid levels on newly identified carotid plaque in middle-aged and elderly Chinese population].

OBJECTIVE: To evaluate the prediction value of blood lipid levels on the newly-identified carotid plaque in middle-aged and elderly Chinese population. METHODS: All study subjects were recruited from two cohorts from 2002 to 2007 [the People's Republic of China/United States of America collaborative study (USA-PRC study) and the Chinese multi-provincial cohort study (CMCS)]. The baseline examination including cardiovascular disease risk factors and B-mode ultrasound of carotid artery was performed in 2002 and the second examination was made in September to October, 2007. The relationship between baseline lipids and carotid plaque incidence was analyzed in a total of 2000 subjects aged 47 to 79 years (mean 63 years). RESULTS: (1) During these 5 years, the prevalence of carotid plaque increased from 30.3% to 62.2% and from 21.5% to 51.5% for men and women, respectively. The newly-identified carotid plaque incidence was 41.8% for men and 34.1% for women. (2) The incidence of artery plaque significantly increased in both sexes in proportion to increase of baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and total to high-density cholesterol ratio (TC/HDL-C) levels (P < 0.05 or P < 0.01). (3) Cross-stratification analysis of LDL-C, triglyceride (TG) and HDL-C for carotid plaque incidence indicated the existence of conjoint effects between LDL-C and HDL-C, LDL and TG, as well as between TG and HDL-C, on the increased incidence of carotid plaque. (4) Multi-factorial analysis showed that higher LDL-C, non-HDL-C and TC/HDL-C were independent risk factors for development of new carotid plaque [OR = 1.44 (95%CI = 1.07 - 1.94), OR = 1.45 (95% CI = 1.08 - 1.96), OR = 1.59(95% CI = 1.14 - 2.23) in men;OR = 1.47 (95% CI = 1.13 - 1.92), OR = 1.35 (95% CI = 1.04 - 1.75), OR = 1.64 (95% CI = 1.20 - 2.23) in women]. CONCLUSIONS: The prevalence of carotid plaque increased rapidly in this cohort between 2002 and 2007. Elevated LDL-C, non-HDL-C and TC/HDL-C levels were independent predictors of newly developed carotid plaque.

2-(1,3-Dithian-2-yl-idene)-1-phenyl-butane-1,3-dione.

The title compound, C(13)H(12)O(2)S(2), belonging to the group of dioxoketene cyclic S,S-acetals, was prepared from the corresponding dione in high yield. In the structure, the C=O and C=C bonds are not coplanar, with O=C-C=C torsion angles of -36.8 (4) and -21.0 (4)°. The dithian ring has a twisted conformation.

[Correlation between serum uric acid and insulin resistance].

OBJECTIVE: To assess the correlation between serum uric acid and insulin resistance in natural population of Beijing. METHODS: 1 056 people without-diabetes, 460 males and 596 females, aged 35-64 was selected from the natural population in Beijing using stratified-random sampling method. Serum uric acid, fasting blood glucose, insulin and other metabolic parameters were measured. The insulin activity index (IAI) was calculated to assess insulin resistance. RESULTS: The natural logarithm of IAI was decreased with the elevation of serum uric acid level (F = 47.884, P < 0.001). The prevalence of insulin resistance increased with the elevation of uric acid level, from 13.8% in quartile 1 to 33.9% in quartile 4. Compared to the quartile 1, the odds ratio (OR) of the quartile 2 for prevalence of insulin resistance was 1.935; the OR of the quartile 3 was 1.590; the OR of the quartile 4 was 2. 088. Uric acid was independently correlated with insulin resistance after adjustment for sex, age and main components of metabolic syndrome (MS). CONCLUSION: Serum uric acid is correlated with insulin resistance in Beijing natural population after adjustment of sex, age, and the main components of MS.

Poly[methano-ltetra-kis[µ(3)-5-(4-methoxy-phen-yl)pyrazole-3-carboxyl-ato(2-)]tri-copper(II)disodium(I).

The asymmetric unit of the polymeric title complex, [Cu(3)Na(2)(C(11)H(8)N(2)O(3))(4)(CH(4)O)](n), consists of two Na(I) atoms, three Cu(II) atoms, four 5-(4-methoxy-phen-yl)pyrazole-3-carboxyl-ate ligands and one methanol mol-ecule. The central Cu(II) atom is coordinated by four N atoms from four pyrazole-3-carboxyl-ate ligands, forming a distorted tetra-hedral (CuN(4)) geometry, while each of the other two Cu(II) atoms is coordinated by two O atoms and two N atoms from the two ligands, forming a slightly distorted square-planar (CuN(2)O(2)) geometry. Each of the two Na(I) atoms is coordinated by five O atoms, forming a distorted octahedral geometry; four O atoms are from the carboxyl-ate groups of the three ligands and the remaining O atom is from the meth-oxy group of the ligand or from the methanol mol-ecule.

Cardiac myxoma and myxosarcoma: clinical experience and immunohistochemistry.

From January 1978 to February 1999, 120 patients (42 males and 78 females) with cardiac myxoma (115) or myxosarcoma (5) underwent surgical excision or biopsy. There were 5 early postoperative deaths (mortality, 4.2%). Seventy-three survivors were followed up for 0.75 to 20.25 years (mean, 9.42 years); they comprised 4 myxosarcoma patients who all had recurrence or metastasis, and 69 myxoma patients who had no evidence of recurrence or metastasis. Neither familial myxoma nor Carney complex was found. The 5 cases of myxosarcoma and 18 randomly selected cases of myxoma were evaluated for proliferative activity, metastatic potential, and oncogene products by immunohistochemistry. The expression of p53 and Bcl-2 was similar in both groups. Overexpression of proliferating cell nuclear antigen and low expression of nm23 in myxosarcoma are consistent with the high rate of recurrence and metastasis of this tumor. Surgical resection of sporadic myxoma is a safe and effective treatment with satisfactory early and long-term results. However, the prognosis of myxosarcoma is still disappointing. Regular echocardiography and chest radiography or computed tomography are necessary for early detection of recurrence or metastasis of myxosarcoma.