Asymmetric Rubottom-Type Oxidation Catalyzed by Chiral Calcium Phosphates.

Invited for the cover of this issue is the group of Jon C. Antilla at Zhejiang Sci-Tech University. The image depicts asymmetric Rubottom-type oxidation catalyzed by chiral calcium phosphates. Read the full text of the article at 10.1002/chem.202203720.

Asymmetric Rubottom-Type Oxidation Catalyzed by Chiral Calcium Phosphates.

A highly efficient catalytic asymmetric Rubottom-type oxidation is described. Using meta-chloroperbenzoic acid (m-CPBA) as the oxidant and chiral calcium phosphate as the catalyst, the facile transformation enables direct hydroxylation of N-Boc oxindoles and ß-ketoesters in high yields (up to 99 %) and in a highly enantioenriched fashion (up to >99 % ee). The application of the established method was demonstrated by the synthesis of a pharmaceutically important 3-hydroxyoxindole with excellent enantiocontrol.

Using Machine Learning Methods to Assess Lymphovascular Invasion and Survival in Breast Cancer: Performance of Combining Preoperative Clinical and MRI Characteristics.

BACKGROUND: Preoperative assessment of lymphovascular invasion (LVI) in invasive breast cancer (IBC) is of high clinical relevance for treatment decision-making and prognosis. PURPOSE: To investigate the associations of preoperative clinical and magnetic resonance imaging (MRI) characteristics with LVI and disease-free survival (DFS) by using machine learning methods in patients with IBC. STUDY TYPE: Retrospective. POPULATION: Five hundred and seventy-five women (range: 24-79 years) with IBC who underwent preoperative MRI examinations at two hospitals, divided into the training (N = 386) and validation datasets (N = 189). FIELD STRENGTH/SEQUENCE: Axial fat-suppressed T2-weighted turbo spin-echo sequence and dynamic contrast-enhanced with fat-suppressed T1-weighted three-dimensional gradient echo imaging. ASSESSMENT: MRI characteristics (clinical T stage, breast edema score, MRI axillary lymph node status, multicentricity or multifocality, enhancement pattern, adjacent vessel sign, and increased ipsilateral vascularity) were reviewed independently by three radiologists. Logistic regression (LR), eXtreme Gradient Boosting (XGBoost), k-Nearest Neighbor (KNN), and Support Vector Machine (SVM) algorithms were used to establish the models by combing preoperative clinical and MRI characteristics for assessing LVI status in the training dataset, and the methods were further applied in the validation dataset. The LVI score was calculated using the best-performing of the four models to analyze the association with DFS. STATISTICAL TESTS: Chi-squared tests, variance inflation factors, receiver operating characteristics (ROC), Kaplan-Meier curve, log-rank, Cox regression, and intraclass correlation coefficient were performed. The area under the ROC curve (AUC) and hazard ratios (HR) were calculated. A P-value <0.05 was considered statistically significant. RESULTS: The model established by the XGBoost algorithm had better performance than LR, SVM, and KNN models, achieving an AUC of 0.832 (95% confidence interval [CI]: 0.789, 0.876) in the training dataset and 0.838 (95% CI: 0.775, 0.901) in the validation dataset. The LVI score established by the XGBoost model was an independent indicator of DFS (adjusted HR: 2.66, 95% CI: 1.22-5.80). DATA CONCLUSION: The XGBoost model based on preoperative clinical and MRI characteristics may help to investigate the LVI status and survival in patients with IBC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

MRI characteristics of breast edema for assessing axillary lymph node burden in early-stage breast cancer: a retrospective bicentric study.

OBJECTIVES: To investigate whether breast edema characteristics at preoperative T2-weighted imaging (T2WI) could help evaluate axillary lymph node (ALN) burden in patients with early-stage breast cancer. METHODS: This retrospective study included women with clinical T1 and T2 stage breast cancer and preoperative MRI examination in two independent cohorts from May 2014 to December 2020. Low (< 3 LNs+) and high (≥ 3 LNs+) pathological ALN (pALN) burden were recorded as endpoint. Breast edema score (BES) was evaluated at T2WI. Univariable and multivariable analyses were performed by the logistic regression model. The added predictive value of BES was examined utilizing the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 1092 patients were included in this study. BES was identified as the independent predictor of pALN burden in primary (n = 677) and validation (n = 415) cohorts. The analysis using MRI-ALN status showed that BES significantly improved the predictive performance of pALN burden (AUC: 0.65 vs 0.71, p < 0.001; IDI = 0.045, p < 0.001; continuous NRI = 0.159, p = 0.050). These results were confirmed in the validation cohort (AUC: 0.64 vs 0.69, p = 0.009; IDI = 0.050, p < 0.001; continuous NRI = 0.213, p = 0.047). Furthermore, BES was positively correlated with biologically invasive clinicopathological factors (p < 0.05). CONCLUSIONS: In individuals with early-stage breast cancer, preoperative MRI characteristics of breast edema could be a promising predictor for pALN burden, which may aid in treatment planning. KEY POINTS: • In this retrospective study of 1092 patients with early-stage breast cancer from two cohorts, the MRI characteristic of breast edema has independent and additive predictive value for assessing axillary lymph node burden. • Breast edema characteristics at T2WI positively correlated with biologically invasive clinicopathological factors, which may be useful for preoperative diagnosis and treatment planning for individual patients with breast cancer.

Coupling Effect of Non-Ignition Impact and Heat on the Decay of FOX-7.

Non-ignition impact and heat stimuli are the most common external stimuli loaded on energetic materials. Nevertheless, there is thereby an urgent need, but it is still a significant challenge to comprehend their coupling effects on the decay and safety mechanisms of energetic materials. Then, reactive molecular dynamics simulation was employed to mimic practical situations and reveal the impact heat coupling effect on the decay mechanism of FOX-7. The temperature and the degree of compression of the crystal caused by the impact are considered variables in the simulation. Both increasing the degree of compression and elevating the temperature promotes the decay of FOX-7. However, their underlying response mechanism is not the same. The acceleration of decomposition is due to the elevated potential energy of the FOX-7 molecules because of elevating the temperature. In addition to the elevated potential energy of the molecule, the main contribution to the decomposition from the compression is to change the decomposition path. The results of the analysis show that compression reduces the stability of the C=C bond, so that chemical reactions related to the double bond occur. In addition, interestingly, the compression along the c direction has an almost equal effect on the final product as the compression along the b direction. Finally, the decay reaction networks are proposed to provide insights into the decomposition mechanism on atomic level. All these findings are expected to pave a way to understand the underlying response mechanism for the FOX-7 against external stimuli.

Mitoxantrone- and Folate-TPGS2k Conjugate Hybrid Micellar Aggregates To Circumvent Toxicity and Enhance Efficiency for Breast Cancer Therapy.

Mitoxantrone (MTO) is a potent drug used to treat breast cancer; however, efforts to expand its clinical applicability have been restricted because of its high risk for cardiotoxicity. In this study, we successfully conjugated MTO or folic acid (FA) to a synthesized D-α-tocopheryl polyethylene glycol 2000 succinate (TPGS2k), herein, shortened to MCT and FCT, respectively. The two produced conjugates could self-assemble to form MCT micelles or MCT/FCT mixed micelles (FMCT) aiming to lower systemic toxicity, enhance entrapment efficiency, and provide a platform for targeted delivery. Moreover, these micellar materials showed a significantly low CMC and could be used to load MTO. The diameters of MTO-loaded micelles (MTO-MCT and MTO-FMCT) were less than 100 nm with a negative zeta potential. We further characterized the pH-responsive drug release of MTO-MCT and MTO-FMCT and then assessed their cellular uptake and antitumor efficacy in human breast cancer cell lines (MCF-7) via confocal microscopy, flow cytometry, and cytotoxicity studies. All the results revealed that both MTO-MCT and MTO-FMCT increased drug loading and entrapment efficiency and possessed sufficient pH-sensitive release. Additionally, MTO-FMCT displayed an improved uptake through folate-mediated endocytosis, resulting in a higher cytotoxic effect on MCF-7 cells compared with that of MTO-MCT. Meanwhile, both MTO-MCT and MTO-FMCT exhibited a low toxicity on hCMEC/D3 normal cells. More importantly, pharmacokinetic study demonstrated that, in comparison with free MTO injection, MTO-MCT and MTO-FMCT, respectively, achieved half-lives 11.5 and 13 times longer and a 9.7- and 5.8-fold increase in AUC. In vivo, both MTO-MCT and MTO-FMCT formulations significantly prolonged the survival time of MCF-7 tumor-bearing mice and had a better efficacy/toxicity ratio. Promisingly, MTO-FMCT micelles remarkably increased MTO accumulation in tumors in vivo, induced higher tumor cell apoptosis, and showed lower toxicity toward major organs. These results imply that MTO-FMCT may be used as a potential drug delivery system for breast cancer targeted therapy.

Catalytic Asymmetric Desymmetrization of Cyclic 1,3-Diketones Using Chiral Boro-phosphates.

Herein, we report a chiral boro-phosphate-catalyzed reductive amination for the desymmetrization of 2,2-disubstituted 1,3-cyclopentadiones with pinacolborane as the reducing agent, delivering chiral ß-amino ketones with an all-carbon quaternary stereocenter in good yields (≤94%), high enantioselectivities (≤97% ee), and excellent diastereoselectivities (>20:1 dr). This reaction has a broad substrate scope and high functional group tolerance. The importance of the chiral products was also demonstrated through the preparation of multifunctional building blocks and heterocycles.

Influence of calcium ions on rhamnolipid and rhamnolipid/anionic surfactant adsorption and self-assembly.

The impact of Ca(2+) counterions on the adsorption at the air-water interface and self-assembly in aqueous solution of the rhamnolipid biosurfactant and its mixture with the anionic surfactant sodium dodecylbenzenesulfonate, LAS, has been studied using neutron reflectometry and small-angle neutron scattering. The results illustrate how rhamnolipids are calcium tolerant and how their blending with conventional anionic surfactants improves the calcium tolerance of the anionic surfactant. Ca(2+) has relatively little effect upon the adsorption and self-assembly of the monorhamnose, R1, and dirhamnose, R2, rhamnolipids, even at high pH, due to their predominantly nonionic nature. For R1/R2 mixtures the addition of Ca(2+) has little impact upon the adsorbed amount or the surface composition. For R2/LAS mixtures the addition of Ca(2+) results in an increased adsorption and a surface slightly richer in R2. The weak binding of Ca(2+) to R1 and R2 does result in a change to the degree of ionization of the micelles and especially for mixed R1/R2 micelles at R1-rich solution compositions. The stronger binding of Ca(2+) to LAS results in the addition of Ca(2+) having a much greater impact on the self-assembly of R1/LAS and R2/LAS mixtures. For R1/LAS mixtures the addition of Ca(2+) promotes the formation of more planar structures, even at low surfactant concentrations where in the absence of Ca(2+) mixed globular micelle formation dominates. In R2/LAS mixtures, where there is a greater contrast between the high and low preferred curvatures associated with R2 and LAS, the addition of Ca(2+) results in a more complex evolution in micellar aggregation and the degree of ionization of the micelles. This results in variations in Ca(2+) binding that promotes micellar structures in which a spatial segregation of the two surfactant components within the micelle occurs.

Pharmacokinetics of orally disintegrating tablets of perphenazine/hydroxypropyl-beta-cyclodextrin inclusion complex in rabbits.

We investigated the pharmacokinetic behavior of orally disintegrating tablets (ODTs) containing perphenazine/hydroxypropyl-beta-cyclodextrin inclusion complex (PPZ/HP-beta-CD) in rabbits and evaluated their bioequivalence with conventional tablets. In this study, a simple, sensitive and accurate high performance liquid chromatography method was developed for the determination of perphenazine concentration in rabbit plasma. The pharmacokinetic parameters were calculated by non-compartmental methods and the bioequivalence between PPZ/HP-beta-CD ODTs with conventional tablets was determined by calculating 90% confidence interval (CI) for the ratio of logarithmic transformed C(max), AUC(0-t), AUC(0-infinity) values. The pharmacokinetic parameters of test ODTs and reference tablets were as follows: C(max), 82.86 and 62.71 ng/mL; AUC(0-24), 480 and 397.56 ng/mL/h; AUC(0-infinity), 505 and 400.12 ng/mL/h; T(max), 1.04 and 3.83h. The relative bioavailabilities of two formulations for AUC(0-t) and AUC(0-infinity) were 120.77% and 126.37%, respectively. The 90% CI statistical analysis demonstrated the two formulations were not bioequivalence. In conclusion, the ODTs showed faster absorption and higher peak concentration when compared with conventional tablets, which suggests ODTs could be promising oral formulations for PPZ.

The value of ultrasound measurement of muscle thickness at different sites and shear wave elastography in Parkinson's disease with sarcopenia: a pilot study.

Background: Patients with Parkinson's disease (PD) and sarcopenia often exhibit resilience, frailty, disability, and depression, highlighting the complex and interrelated nature of these conditions. Objective: Despite the presence of clinical manifestations of muscle atrophy in both PD and sarcopenia, accurately discerning the coexistence of sarcopenia in PD patients remains a challenging task with significant implications for treatment strategies and prognostic assessments. This study aims to elucidate the specific ultrasonic diagnostic parameters associated with PD accompanied by sarcopenia through a comparative analysis of muscle ultrasound parameters in patients with PD, thereby presenting a novel approach for rapid identification of this condition. Methods: A total of 110 participants were enrolled in this study, including patients with PD and control subjects. Demographic data, clinical characteristics, physical performance tests, appendicular skeletal muscle mass index (ASMI), bioelectrical impedance analysis and muscle ultrasound measurements were collected from all participants. The muscle ultrasound measurements encompassed assessments of muscle thickness, pennation angle and shear wave elastography at various anatomical sites. Results: Parkinson's disease patients exhibited decreased muscle strength and physical performance, and increased shear wave elastography value. In PD patients with sarcopenia, body circumference, including calf circumference, mid-arm circumference, Waist-to-Hip Ratio and body mass index (BMI) were all significantly decreased. Biceps brachii muscle thickness (MT) and gastrocnemius MT decreased in PD patients with sarcopenia and low ASMI. Binary logistic regression analysis revealed that male PD patients, BMI and gastrocnemius MT were predictive factors for ASMI in PD patients. Conclusion: Biceps brachii MT and gastrocnemius MT are important indicators for distinguishing whether PD patients have sarcopenia. Male patients, low BMI and gastrocnemius MT were identified as valid predictors of low ASMI in PD patients. The findings of this study provide important insights into the use of muscle ultrasound in the diagnosis of PD with sarcopenia.

Value of mammographic microcalcifications and MRI-enhanced lesions in the evaluation of residual disease after neoadjuvant therapy for breast cancer.

Background: Microcalcifications persist even if a patient with breast cancer achieves pathologic complete response (pCR) as confirmed by surgery after neoadjuvant treatment (NAT). In practice, surgeons tend to remove all the microcalcifications. This study aimed to explore the correlation between changes in the extent of microcalcification after NAT and pathological tumor response and compare the accuracy of mammography (MG) and magnetic resonance imaging (MRI) in predicting the size of residual tumors. Methods: This was a retrospective study which included a consecutive series of patients in Guangdong Provincial People's Hospital. Between January 2010 and January 2020, 127 patients with breast cancer and Breast Imaging Reporting and Data System (BI-RADS) 4-5 microcalcifications were included in this study. The maximum diameter of the microcalcifications on MG and lesion enhancement on MRI pre- and post-NAT were measured. The correlations between the changes in residual microcalcifications on MG and pCR were analyzed. Intraclass correlation coefficients (ICCs) were computed between the extent of the residual microcalcifications, residual enhancement, and residual tumor size. Results: There were no statistically significant differences in the changes in microcalcifications after NAT according to the RECIST criteria on MRI (P=0.09) and Miller-Payne grade (P=0.14). MRI showed a higher agreement than did residual microcalcifications on MG in predicting residual tumor size (ICC: 0.771 vs. 0.097). Conclusions: MRI is more accurate for evaluating residual tumor size in breast cancer. In our study, the extent of microcalcifications on MG after NAT had nearly no correlation with the pathological size of the residual tumor. Therefore, residual tumors with microcalcifications may not necessarily be a contraindication to breast-conserving surgery.

Use of Pretreatment Multiparametric MRI to Predict Tumor Regression Pattern to Neoadjuvant Chemotherapy in Breast Cancer.

RATIONALE AND OBJECTIVES: To develop an easy-to-use model by combining pretreatment MRI and clinicopathologic features for early prediction of tumor regression pattern to neoadjuvant chemotherapy (NAC) in breast cancer. MATERIALS AND METHODS: We retrospectively analyzed 420 patients who received NAC and underwent definitive surgery in our hospital from February 2012 to August 2020. Pathologic findings of surgical specimens were used as the gold standard to classify tumor regression patterns into concentric and non-concentric shrinkage. Morphologic and kinetic MRI features were both analyzed. Univariable and multivariable analyses were performed to select the key clinicopathologic and MRI features for pretreatment prediction of regression pattern. Logistic regression and six machine learning methods were used to construct prediction models, and their performance were evaluated with receiver operating characteristic curve. RESULTS: Two clinicopathologic variables and three MRI features were selected as independent predictors to construct prediction models. The apparent area under the curve (AUC) of seven prediction models were in the range of 0.669-0.740. The logistic regression model yielded an AUC of 0.708 (95% confidence interval [CI]: 0.658-0.759), and the decision tree model achieved the highest AUC of 0.740 (95% CI: 0.691-0.787). For internal validation, the optimism-corrected AUCs of seven models were in the range of 0.592-0.684. There was no significant difference between the AUCs of the logistic regression model and that of each machine learning model. CONCLUSION: Prediction models combining pretreatment MRI and clinicopathologic features are useful for predicting tumor regression pattern in breast cancer, which can assist to select patients who can benefit from NAC for de-escalation of breast surgery and modify treatment strategy.

Gender-specific impact of cognitive impairment on all-cause mortality in older persons: A meta-analysis.

BACKGROUND: Gender-specific impact of cognitive impairment on survival in the general population remains controversial. The objective of this meta-analysis was to assess the gender difference in the impact of cognitive impairment on all-cause mortality in the general population. METHODS: Two reviewers independently searched PubMed and Embase databases up to September 30, 2021 for cohort studies that reported gender-specific impact of cognitive impairment detected by the mini-mental state examination (MMSE) on all-cause mortality in elderly general population (aged ≥60 years) in the same study. RESULTS: Nine articles reporting on 10 studies with a total of 52,134 individuals were included. The pooled multivariate-adjusted risk ratio (RR) of all-cause mortality associated with cognitive impairment compared with those without was 1.48 (95% confidence interval [CI] 1.36-1.61) in women and 1.34 (95% CI 1.24-1.44) in men, after adjusting for potential confounding. The pooled multivariate-adjusted female-to-male ratio of relative risk of all-cause mortality was 1.08 (95% CI 1.02-1.14) for individuals with cognitive impairment versus those without. CONCLUSIONS: Cognitive impairment detected by the MMSE is associated with an increased risk of all-cause mortality in older aged women than in men from the general population, even after adjusting sociodemographic factors. Compared with men with cognitive impairment, women with cognitive impairment had an 8% higher risk of all-cause mortality. These findings highlight the importance of early detection and management of cognitive impairment in older adults, particularly in women.

Asymmetric Reductive Amination with Pinacolborane Catalyzed by Chiral SPINOL Borophosphates.

The catalytic asymmetric reductive amination of ketones with pinacolborane employing chiral SPINOL-derived borophosphates as catalysts has been realized. A series of chiral amine derivatives bearing multiple functional groups were obtained in good to excellent yields and enantioselectivities (up to 97% yield, 98% ee) under mild reaction conditions. Moreover, the synthetic applicability of the established method has been demonstrated by the asymmetric synthesis of (R)-Fendiline.

Multiple-parameter MRI after neoadjuvant systemic therapy combining clinicopathologic features in evaluating axillary pathologic complete response in patients with clinically node-positive breast cancer.

OBJECTIVE: This study aimed to evaluate axillary pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) in clinically node-positive breast cancer (BC) patients based on post-NST multiple-parameter MRI and clinicopathological characteristics. METHODS: In this retrospective study, females with clinically node-positive BC who received NST and followed by surgery between January 2017 and September 2021 were included. All axillary lymph nodes (ALNs) on MRI were matched with pathology by ALN markers or sizes. MRI morphological parameters, signal intensity curve (TIC) patterns and apparent diffusion coefficient (ADC) values of post-NST ALNs were measured. The clinicopathological characteristics was also collected and analyzed. Univariable and multivariable logistic regression analyses were performed to evaluate the independent predictors of axillary pCR. RESULTS: Pathologically confirmed 137 non-pCR ALNs in 71 patients and 87 pCR ALNs in 87 patients were included in this study. Cortical thickness, fatty hilum, and TIC patterns of ALNs, hormone receptor, and human epidermal growth factor receptor 2 (HER2) status were significantly different between the two groups (all, p < 0.05). There was no significant difference for ADC values (p = 0.875). On multivariable analysis, TIC patterns (odds ratio [OR], 2.67, 95% confidence interval [CI]: 1.33, 5.34, p = 0.006), fatty hilum (OR, 2.88, 95% CI:1.39, 5.98, p = 0.004), hormone receptor (OR, 8.40, 95% CI: 2.48, 28.38, p = 0.001) and HER2 status (OR, 8.57, 95% CI: 3.85, 19.08, p < 0.001) were identified as independent predictors associated with axillary pCR. The area under the curve of the multivariate analysis using these predictors was 0.85 (95% CI: 0.79, 0.91). CONCLUSION: Combining post-NST multiple-parameter MRI and clinicopathological characteristics allowed more accurate identification of BC patients who had received axillary pCR after NST. ADVANCES IN KNOWLEDGE: A combined model incorporated multiple-parameter MRI and clinicopathologic features demonstrated good performance in evaluating axillary pCR preoperatively and non-invasively.

Adsorption of sophorolipid biosurfactants on their own and mixed with sodium dodecyl benzene sulfonate, at the air/water interface.

The adsorption of the lactonic (LS) and acidic (AS) forms of sophorolipid and their mixtures with the anionic surfactant sodium dodecyl benzene sulfonate (LAS) has been measured at the air/water interface by neutron reflectivity, NR. The AS and LS sophorolipids adsorb with Langmuir-like adsorption isotherms. The more hydrophobic LS is more surface active than the AS, with a lower critical micellar concentration, CMC, and stronger surface adsorption, with an area/molecule ∼70 Å(2) compared with 85 Å(2) for the AS. The acidic sophorolipid shows a maximum in its adsorption at the CMC which appears to be associated with a mixture of different isomeric forms. The binary LS/AS and LS/LAS mixtures show a strong surface partitioning in favor of the more surface active and hydrophobic LS component but are nevertheless consistent with ideal mixing at the interface. In contrast, the surface composition of the AS/LAS mixture is much closer to the solution composition, but the surface mixing is nonideal and can be accounted for by regular solution theory, RST. In the AS/LS/LAS ternary mixtures, the surface adsorption is dominated by the sophorolipid, and especially the LS component, in a way that is not consistent with the observations for the binary mixtures. The extreme partitioning in favor of the sophorolipid for the LAS/LS/AS (1:2) mixtures is attributed to a reduction in the packing constraints at the surface due to the AS component. Measurements of the surface structure reveal a compact monolayer for LS and a narrow solvent region for LS, LS/AS, and LS/LAS mixtures, consistent with the more hydrophobic nature of the LS component. The results highlight the importance of the relative packing constraints on the adsorption of multicomponent mixtures, and the impact of the lactonic form of the sophorolipid on the adsorption of the sophorolipid/LAS mixtures.

Solution self-assembly of the sophorolipid biosurfactant and its mixture with anionic surfactant sodium dodecyl benzene sulfonate.

The self-assembly in aqueous solution of the acidic (AS) and lactonic (LS) forms of the sophorolipid biosurfactant, their mixtures, and their mixtures with anionic surfactant sodium dodecyl benzene sulfonate, LAS, has been studied using predominantly small-angle neutron scattering, SANS, at relatively low surfactant concentrations of <30 mM. The more hydrophobic lactonic sophorolipid forms small unilamellar vesicles at low surfactant concentrations, in the concentration range of 0.2 to 3 mM, and transforms via a larger unilamellar vesicle structure at 7 mM to a disordered dilute phase of tubules at higher concentrations, 10 to 30 mM. In marked contrast, the acidic sophorolipid is predominantly in the form of small globular micelles in the concentration range of 0.5 to 30 mM, with a lower concentration of larger, more planar aggregates (lamellar or vesicular) in coexistence. In mixtures of AS and LS, over the same concentration range, the micellar structure associated with the AS sophorolipid dominates the mixed-phase behavior. In mixtures of anionic surfactant LAS with the AS sophorolipid, the globular micellar structure dominates over the entire composition and concentration range studied. In contrast, mixtures of LAS with the LS sophorolipid exhibit a rich evolution in phase behavior with solution composition and concentration. At low surfactant concentrations, the small unilamellar vesicle structure present for LS-rich solution compositions evolves into a globular micelle structure as the solution becomes richer in LAS. At higher surfactant concentrations, the disordered lamellar structure present for LS-rich compositions transforms to small vesicle/lamellar coexistence, to lamellar/micellar coexistence, to micellar/lamellar coexistence, and ultimately to a pure micellar phase as the solution becomes richer in LAS. The AS sophorolipid surfactant exhibits self-assembly properties similar to those of most other weakly ionic or nonionic surfactants that have relatively large headgroups. However, the more hydrophobic nature of the lactonic sophorolipid results in a more complex and unusual evolution in phase behavior with concentration and with concentration and composition when mixed with anionic surfactant LAS.

Capillary electrophoresis method for the determination of flavonoids.

Due to their biological and physiological importance, flavonoids received considerable attention in the literature. This review discusses the widely used analytical method i.e. capillary electrophoresis (CE) including the chiral flavonoids separation and the hyphenation of CE and MS. Techniques used for enhancement of sensitivity such as stacking, sweeping, isotachophoresis etc. were also discussed.

[Pharmacokinetics of brucine in rats after intravenous administration of liposomes containing total alkaloids from seed of Strychnos nux-vomica].

OBJECTIVE: To compare the pharmacokinetic characteristics of brucine following intravenous administration of liposomes, containing total alkaloids from seed of Strychnos nux-vomica, to rats with different phospholipids composition. METHOD: Liposomes containing the total alkaloids were prepared by the method of ammonium sulfate transmembrane gradients and stealth liposome technique. The contents of total alkaloids and brucine in liposomes were determined and compared after free drug being removed. After intravenous administration of total alkaloids solution or liposomes with different composition, plasma samples were drawn at predetermined time points and the concentrations of brucine were determined by a validated method of HPLC. Pharmacokinetic analysis was performed by 3P97 program. RESULT: The ratios of brucine to total alkaloids in liposomes hardly varied with phospholipids composition. Compared with SPC liposome, AUC of brucine was increased 13.3-fold and apparent volume of distribution was decreased to only 3.6% following intravenous administration of HSPC liposome. In addition, besides that AUC of brucine was slightly increased, most pharmacokinetic parameters were not significantly changed after administration of the novel liposome compared with those of SPC liposome. CONCLUSION: Phospholipids composition has a significant influence on the pharmacokinetics of brucine after intravenous administration of liposomes containing total alkaloids from seed of S. nux-vomica.