An efficient method for the preparative isolation and purification of alkaloids from Gelsemium by using high speed counter-current chromatography and preparative HPLC.

We established an efficient method using high-speed countercurrent chromatography (HSCCC) combined with preparative high-performance liquid chromatography (prep-HPLC) for isolating and purifying Gelsemium elegans (G. elegans) alkaloids. First, the two-phase solvent system composed of 1% triethylamine aqueous solution/n-hexane/ethyl acetate/ethanol (volume ratio 4:2:3:2) was employed to separate the crude extract (350 mg) using HSCCC. Subsequently, the mixture that resulted from HSCCC was further separated by Prep-HPLC, resulting in seven pure compounds including: 14-hydroxygelsenicine (1, 12.1 mg), sempervirine (2, 20.8 mg), 19-(R)-hydroxydihydrogelelsevirine (3, 10.1 mg), koumine (4, 50.5 mg), gelsemine (5, 32.2 mg), gelselvirine (6, 50.5 mg), and 11-hydroxyhumanmantenine (7, 12.5 mg). The purity of these seven compounds were 97.4, 98.9, 98.5, 99, 99.5, 96.8, and 85.5%, as determined by HPLC. The chemical structures of the seven compounds were analyzed and confirmed by electrospray ionization mass spectrometry (ESI-MS), 1H-nuclear magnetic resonance (1H NMR), and 13 C-nuclear magnetic resonance (13 C NMR) spectra. The results indicate that the HSCCC-prep-HPLC method can effectively separate the major alkaloids from the purified G. elegans, holding promising prospects for potential applications in the separation and identification of other traditional Chinese medicines.

A Rotating Triboelectric Nanogenerator Driven by Bidirectional Swing for Water Wave Energy Harvesting.

Due to the simple installation and convenient maintenance, the floating water wave energy harvesting devices have significant economic advantages. Mass power density is the most important index to evaluate the advancement of floating wave energy harvesting devices. Herein, a self-adaptive rotating triboelectric nanogenerator (SR-TENG) with a compound pendulum and a functional gear-set is provided for wave energy harvesting. First, a compound pendulum structure with a low center of gravity and high moment of inertia is obtained by the geometric design and mechanical study. Besides, compared with the previous triboelectric nanogenerator with one-way clutch, SR-TENG can harvest twice the kinetic energy utilization through the functional gear-set. Importantly, depending on the structure design, the SR-TENG obtains the average mass power density of 45.18 mW kg-1 under low frequency driving conditions, which is about 10 times the reference electromagnetic generator with a similar structure and size. This result shows that the SR-TENG has a significant advantage in small water wave energy harvesting. These findings provide an important example of the floating water wave energy harvesting devices.

Comparative metabolism of gelsenicine in liver microsomes from humans, pigs, goats and rats.

RATIONALE: Gelsemium elegans (G. elegans) is highly toxic to humans and rats but has insecticidal and growth-promoting effects on pigs and goats. However, the mechanisms behind the toxicity differences of G. elegans are unclear. Gelsenicine, isolated from G. elegans, has been reported to be a toxic alkaloid. METHODS: In this study, the in vitro metabolism of gelsenicine was investigated and compared for the first time using human (HLM), pig (PLM), goat (GLM) and rat (RLM) liver microsomes and high-performance liquid chromatography/mass spectrometry (HPLC/MS). RESULTS: In total, eight metabolites (M1-M8) were identified by using high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). Two main metabolic pathways were found in the liver microsomes of the four species: demethylation at the methoxy group on the indole nitrogen (M1) and oxidation at different positions (M2-M8). M8 was identified only in the GLM. The degradation ratio of gelsenicine and the relative percentage of metabolites produced during metabolism were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/QqQ-MS/MS). The degradation ratio of gelsenicine in liver microsomes decreased in the following order: PLM ≥ GLM > HLM > RLM. The production of M1 decreased in the order of GLM > PLM > RLM > HLM, the production of M2 was similar among the four species, and the production of M3 was higher in the HLM than in the liver microsomes of the other three species. CONCLUSIONS: Based on these results, demethylation was speculated to be the main gelsenicine detoxification pathway, providing vital information to better understand the metabolism and toxicity differences of G. elegans among different species.

Fast lithography aerial image calculation method based on machine learning.

Aerial image calculation for thick masks is an indispensable but time-consuming step in most lithography simulations. This paper develops a fast thick-mask aerial image calculation method based on machine learning for partially coherent lithography systems. First, some sparse sampling points are chosen from the source plane to represent the partially coherent illumination. Then, the training libraries of thick-mask diffraction near-fields are built up for all sampling points based on a set of representative mask features. For an arbitrary thick mask, we calculate its aerial image using the nonparametric kernel regression technique and the pre-calculated training libraries. Subsequently, a post-processing method is applied to compensate for the estimation error and improve the computational accuracy. In addition, this paper also studies the impacts of several key factors on the accuracy and efficiency of the proposed method. Finally, the proposed method is verified by the simulations at 45 nm and 14 nm technology nodes.

Targeting of the deubiquitinase USP9X attenuates B-cell acute lymphoblastic leukemia cell survival and overcomes glucocorticoid resistance.

Although previous studies attributed a pro-survival role to USP9X in human cancer, how USP9X affects B-cell acute lymphoblastic leukemia (B-ALL) remains unclear. Here, we found that USP9X is overexpressed in B-ALL cell lines and human patients. We investigated the role of USP9X in B-ALL and found that USP9X knockdown significantly reduced leukemic cell growth and increased spontaneous apoptosis, thereby improving survival in immunodeficient mice. These effects are partially mediated by the intrinsic apoptotic pathway, as we found that USP9X-knockdown leukemic cells displayed MCL1 down-regulation, with decreased BCL-2/BCL-XL levels and increased BAX levels. In addition, we demonstrated that USP9X inhibition negatively regulates mTORC1 activity toward its substrate S6K1. Clinically, USP9X inhibition sensitized glucocorticoid-resistant ALL cells to prednisolone; this observation reveals a potential avenue for improving the treatment of drug-resistant relapses. Collectively, our findings suggest that the combination of USP9X targeting and glucocorticoids treatment has attractive utility in B-ALL. This approach represents a potential strategy for promising combination therapies for lymphoid malignancies.

PP242 synergizes with suberoylanilide hydroxamic acid to inhibit growth of ovarian cancer cells.

OBJECTIVES: Overexpression of histone deacetylases and activation of the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway are common aberrations in ovarian cancer. For this reason, simultaneous inhibition of such targets is a rational therapeutic strategy to treat patients with ovarian cancer. This study aimed to investigate the biological effect of the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), in combination with the dual mTOR complex 1 and mTOR complex 2 inhibitor, PP242, against ovarian cancer cells. MATERIALS AND METHODS: The effects of SAHA and PP242 on the growth of SKOV3 and A2780 cells were examined using Cell Counting Kit-8. The apoptosis was analyzed through flow cytometry, and the expression of apoptosis-related proteins was investigated through Western blotting. Induction of autophagy was determined through fluorescence microscopy using a stably transfected green fluorescent protein/microtubule-associated protein light chain 3 construct to visualize autophagosome formation. The expression of autophagy-related proteins was determined through Western blot analysis. The effect of SAHA and PP242 on the growth of ovarian cancer was also examined in an orthotopic ovarian cancer model. RESULTS: The combination of SAHA and PP242 significantly inhibited cell proliferation and synergistically increased apoptosis and autophagy compared with each agent alone in vitro. In vivo, this combination exhibited greater inhibition on tumor growth than monotreatments did and it significantly prolonged the survival time of the mice. CONCLUSIONS: These results suggest that the combination of SAHA and PP242 may lead to a novel strategy in treating patients with ovarian cancer.

The influence of knowledge-intensive service industry agglomeration in the Yangtze River Delta urban agglomeration on regional economy.

Knowledge-intensive service industry has become an important part of social economy, which not only promotes the innovation of modern service industry, but also promotes the upgrading and transformation of manufacturing industry. The agglomeration of knowledge-intensive service industry is not only the inevitable result of economic growth, but also the premise of sustained economic growth. Moreover, China's national economy is transforming from an industrialized economy to a service-oriented and knowledge-based economy, and the importance of knowledge-intensive service industry is increasing day by day. This paper constructs a theoretical framework of the influence of population agglomeration on the economic development of urban agglomerations. The article holds that population agglomeration promotes the economic development of urban agglomerations through the upgrading of industrial structure and the promotion of human capital. In the future, we need to focus on the similarities and differences between population agglomeration and economic development of urban agglomerations in central China, explore the factors of economic development of urban agglomerations, and provide reasonable suggestions for the government to formulate relevant economic policies. This paper, from an innovative research perspective, based on the perspective of population agglomeration, studies the path of its role in regional economic development, which can make up for this defect to some extent. Moreover, the research object has been innovated and the research method has been improved. On the basis of the above, the panel data of the Yangtze River Delta from 2012 to 2021 is selected as the research sample, the location entropy index is taken as the explanatory variable, the regional gross domestic product (GDP) is taken as the explanatory variable, and the rationality of economic theory and the significance of econometric test are considered. Finally, the data are analyzed and tested by regression. The empirical analysis of the Yangtze River Delta urban agglomeration proves the importance of knowledge-intensive service industry agglomeration to regional economic development. Finally, based on the contribution of knowledge-intensive service industry agglomeration to regional economy, the development of knowledge-intensive service industry and the promotion of industrial agglomeration are studied.

Effects of exercise dose based on the ACSM recommendations on patients with post-stroke cognitive impairment: a systematic review and meta-analyses.

Purpose: This review aimed to assess the impact of different exercise dosages on cognitive function in individuals with post-stroke cognitive impairment (PSCI). Methods: Four electronic databases-Embase, PubMed, Web of Science, and Cochrane Library-were systematically searched from inception to 01 January 2024, focusing on the impact of exercise therapy on cognitive function in individuals with PSCI. Only randomized controlled trials meeting the criteria were included. The exercise therapy dose and adherence were evaluated following the American College of Sports Medicine (ACSM) guidelines, categorized into a high compliance group with ACSM recommendations and a low or uncertain compliance group. A random-effects model compared the effect of ACSM compliance on cognitive function in individuals with PSCI, with the effect size represented by the standardized mean difference (SMD) and a 95% confidence interval (CI). Results: In total, 18 studies meeting the criteria were included, with data from 1,742 participants. The findings suggested a beneficial effect of exercise on cognitive function in individuals with PSCI [SMD = 0.42, 95% CI (0.20, 0.65)]. Ten studies were categorized as the "high adherence group" and eight in the "low or uncertain adherence group" based on the ACSM recommendations. The subgroup analysis revealed that the SMD of the high compliance group was 0.46 (95% CI: 0.10, 0.82) (p = 0.01), while the SMD of the low or uncertain compliance group was 0.38 (95% CI: 0.07, 0.70) (p = 0.02). Conclusion: Our study indicates the beneficial impact of exercise for patients with PSCI over no exercise. Furthermore, high adherence to the exercise dose recommended by ACSM guidelines demonstrated a more substantial improvement in cognitive function than low or uncertain adherence in patients with PSCI. Systematic Review Registration: https:// www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42023487915.

Combination of Simo Decoction and Golden Bifid alleviates functional dyspepsia through a mechanism involving intestinal microbiota and short-chain fatty acids.

BACKGROUND AND STUDY AIMS: The integration of traditional Chinese medicine and Western medicine holds promise for the treatment of gastrointestinal disorders, which are influenced by intestinal microbiota and metabolites. This study reports a possible mechanism for the combination of Simo Decoction and Golden Bifid in functional dyspepsia (FD) by regulating intestinal microbiota and short-chain fatty acids (SCFAs). PATIENTS AND METHODS: A mouse model of food stagnation was constructed and treated with Simo Decoction combined with different concentrations of Golden Bifid. Meta-genomics sequencing was conducted to analyze the cecum contents of the mice. Following analyses of the composition and abundance of intestinal microbiota, gas chromatography-mass spectrometry was performed to measure SCFAs in the colonic content of mice. Finally, ELISA was utilized to determine the levels of pro-inflammatory factors in the duodenal mucosa of mice and the infiltration of eosinophils in the duodenum was observed by immunohistochemical staining. RESULTS: Combination of Simo Decoction and Golden Bifid more significantly alleviated dyspepsia in mice with food stagnation compared with Simo Decoction alone. The optimal ratio of combined treatment was 0.0075 mL/g (body weight) Simo Decoction and 0.0032 mg/g (body weight) Golden Bifid. The combined treatment increased the abundance of Bifidobacterium and Bacteroides in the intestine. The levels of SCFAs in the colonic contents of mice were increased after the combined treatment, contributing to diminished pro-inflammatory factors in the duodenal mucosa and reduced eosinophil infiltration. CONCLUSION: Combination of Simo Decoction and Golden Bifid increases the abundance of Bacteroides and Bifidobacterium and promotes the production of SCFAs, which is instrumental for alleviation of FD.

[Comparative study on rat in situ nasal absorption of geniposide of Xingnaojing nasal drop and Xingnaojing microemulsion].

Xingnaojing (XNJ) is an effective clinical drug used to treat acute stroke. Compared with injection administration, its nasal administration has better brain targeting. Therefore, through nasal administration, XNJ microemulsion could help solve the drug load of compound components of different polarities contained in large-dose and high-concentration traditional Chinese medicines, and reduce irritation to nasal mucosa In this study, the modified volume correction method and the improved rat in situ nasal perfusion model were adopted to compare the nasal absorption of geniposide contained in different XNJ preparations. The results showed that the constant absorption rate of geniposide (GE) in XNJ-D was (2.95 +/- 0.25) x 10(-3) min(-1), whereas the constant absorption rate of GE in XNJ-M was (2.16 +/- 0.21) x 10(-3) min(-1). This indicated that the rat nasal absorption of GE in different XNJ preparations complied with the first-order process and could be considered as passive absorption. GE in XNJ-D was absorbed faster than that in XNJ-M, which provided basis for the development of nasal preparations of XNJ.

Molecular Characterization of Size-Fractionated Humic Acids Derived from Lignite and Its Activation of Soil Legacy Phosphorus and Lactuca sativa Growth-Promoting Performances.

Humic acid (HA) has been widely used in agricultural production processes because it improves soil nutrients and has a growth-promoting effect on plants. Understanding the relationship between the structure and function of HA is the key to efficient utilization of HA in the field of activating soil legacy phosphorus (P) and promoting crop growth. In this work, HA was prepared using lignite as raw materials by the ball milling method. Moreover, a series of HAs with different molecular weights (<10, 10-50, and >50 kDa) were prepared through ultrafiltration membranes. The chemical composition and physical structure characteristics of the prepared HA were tested. The effects of HA with different molecular weights on activating accumulated P in calcareous soil and root promotion of Lactuca sativa were investigated. Results showed that HAs with different molecular weights have different functional group structures, molecular compositions, and micromorphologies, and the molecular weight of HA can significantly affect the activation performance on soil accumulated P. Moreover, the HA with low molecular weight more easily enhanced the seed germination and growth of Lactuca sativa than that of raw HA. It is expected that more efficient HA can be prepared in the future for the activation of accumulated P and promoting crop growth.

Brain-Inspired Search Engine Assistant Based on Knowledge Graph.

Search engines can quickly respond to a hyperlink list according to query keywords. However, when a query is complex, developers need to repeatedly refine search keywords and open a large number of web pages to find and summarize answers. Many research works of question and answering (Q&A) system attempt to assist search engines by providing simple, accurate, and understandable answers. However, without original semantic contexts, these answers lack explainability, making them difficult for users to trust and adopt. In this article, a brain-inspired search engine assistant named DeveloperBot based on knowledge graph is proposed, which aligns to the cognitive process of humans and has the capacity to answer complex queries with explainability. Specifically, DeveloperBot first constructs a multilayer query graph by splitting a complex multiconstraint query into several ordered constraints. Then, it models a constraint reasoning process as a subgraph search process inspired by a spreading activation model of cognitive science. In the end, novel features of the subgraph are extracted for decision-making. The corresponding reasoning subgraph and answer confidence are derived as explanations. The results of the decision-making demonstrate that DeveloperBot can estimate answers and answer confidences with high accuracy. We implement a prototype and conduct a user study to evaluate whether and how the direct answers and the explanations provided by DeveloperBot can assist developers' information needs.

Dose-dense regimen versus conventional three-weekly paclitaxel combination with carboplatin chemotherapy in first-line ovarian cancer treatment: a systematic review and meta-analysis.

BACKGROUND: Paclitaxel dose-dense regimen has been controversial in clinical trials in recent years. This systematic review and meta-analysis tried to evaluate the efficacy and safety of paclitaxel dose-dense chemotherapy in primary epithelial ovarian cancer. METHODS: An electronic search following PRISMA guidelines was conducted (Prospero registration number: CRD42020187622), and then a systematic review and meta-analysis of included literature were initiated to determine which regimen was better. RESULTS: Four randomized controlled trials were included in the qualitative evaluation, and 3699 ovarian cancer patients were included in the meta-analysis. The meta-analysis revealed that the dose-dense regimen could prolong PFS (HR0.88, 95%CI 0.81-0.96; p = 0.002) and OS (HR0.90, 95%CI 0.81-1.02; p = 0.09), but it also increased the overall toxicity (OR = 1.102, 95%CI 0.864-1.405; p = 0.433), especially toxicity of anemia (OR = 1.924, 95%CI 1.548-2.391; p < 0.001), neutropenia (OR = 2.372, 95%CI 1.674-3.361; p < 0.001). Subgroup analysis indicated that the dose-dense regimen could significantly prolong not only PFS (HR0.76, 95%CI 0.63-0.92; p = 0.005 VS HR0.91, 95%CI 0.83-1.00; p = 0.046) but also OS (HR0.75, 95%CI 0.557-0.98; p = 0.037 VS HR0.94, 95%CI 0.83-1.07; p = 0.371) in Asian, and overall toxicity was significantly increased in Asians (OR = 1.28, 95%CI: 0.877-1.858, p = 0.202) compared to non-Asians (OR = 1.02, 95%CI 0.737-1.396, p = 0.929). CONCLUSION: Paclitaxel dose-dense regimen could prolong PFS and OS, but it also increased the overall toxicity. Therapeutic benefits and toxicity of dose-dense are more obvious in Asians compared to non-Asians, which need to be further confirmed in clinical trials.

Bioavailability and brain-targeting of geniposide in gardenia-borneol co-compound by different administration routes in mice.

Both geniposide (Ge) and borneol (Bo) are bioactive substances derived from traditional Chinese medicine. Injections containing co-compound of Gardenia-Borneol are widely used for stroke treatment in China, such as "Xingnaojing" multi-component injection. As more and more adverse reactions (especially drug allergy) were reported, it is urgent to find more effective and safer routes of administration for such kinds of medicines. In this paper, bioavailabilities and brain-target effects of geniposide in Gardenia-Borneol co-compound through different administration routes in mice were investigated. Geniposide concentrations in plasma and in brain of mice were determined by reversed-phase high-performance liquid chromatography. The pharmacokinetics parameters of intranasal (i.n.) and intragastric (i.g.) administration were compared with intravenous (i.v.) administration. The bioavailabilities of Ge were 85.38% and 28.76% for i.n. and i.g. while T(max) were 1 min and 30 min. C(max) were 21.881 ± 5.398, 1.914 ± 0.327 and 42.410 ± 6.268 µg/mL for i.n., i.g. and i.v., respectively. The AUC of Ge in brain were 32413.6 ± 4573.9, 6440.1 ± 863.7 and 37270.5 ± 4160.6 ng/g ·min for i.n., i.g. and i.v., respectively. The drug target indexes (DTI) were 1.02 and 0.60 for i.n. and i.g. The results demonstrated that geniposide could be absorbed promptly and thoroughly by i.n. administration in mice and basically transported into the brain though blood vessel passways.

In situ and in vivo study of nasal absorption of borneol in rats.

The aim of this work was to study the in situ and in vivo nasal absorption of borneol. A novel single pass in situ nasal perfusion technique was applied to examine the rate and extent of nasal absorption of borneol by rats. Experimental conditions, such as perfusion rate, pH and drug concentration, were investigated. The in situ experiments showed that the nasal absorption of borneol was not dependent on drug concentration, and fitted a first order process. The absorption rate constant, Ka, influenced with an increase in perfusion speed. The borneol was well absorbed in the conditions of the nasal cavity within the pH range and pH value of physiological conditions. In vivo studies of borneol absorption were carried out in rats and the pharmacokinetics parameters of intranasal (i.n.) was compared with intravenous (i.v.) administration. The bioavailabilities of borneol was 90.82% for i.n. while Tmax values were 10min. MRT (Mean Residence Time) were 262.55 +/- 67.35 min and 204.22 +/- 14.50 min for i.n. and i.v. methods, respectively. The results demonstrate that borneol could be absorbed promptly and thoroughly by i.n. administration in rats.

Can European Union (EU) Enlargement Boost Regional Economic Common Growth? Multi-Period Difference-in-Difference (DID) Method.

Under the dual background of Britain's blatant "Brexit" and the steady "expansion" of the European Union (EU) audit list, the economic effect of the development of regional alliances, in the end, is a question worthy of in-depth discussion. Using data from a sample of 27 EU member states from 2000 to 2018, this study examines and compares the impact of EU enlargement on economic growth for countries as a whole, developed and developing countries, and Central and Eastern European (CEE) countries using a multi-period difference-in-difference (DID) method and explores the mechanisms underlying that. The results show that EU enlargement contributes to the expected regional economic growth, and the effect is more evident in developed countries and CEE countries; the robustness of the results is tested by the dynamic effect test and counterfactual method; EU enlargement improves the spatial allocation of factor markets through regional integration, increases productivity, and positively promotes the overall national economic growth. As a typical quasi-natural experiment of the development of regional integration, the research results of this study on the enlargement of the EU provide a useful reference for the promotion of the development of cross-administrative integration around the world.

Knockdown of CDCA5 suppresses malignant progression of breast cancer cells by regulating PDS5A.

Breast cancer is one of the most common malignant tumors in women. Cell division cycle­associated 5 (CDCA5) is closely associated with the behavior of various cancer types. The aim of the present study was to explore the effect of CDCA5 on breast cancer. Western blot analysis and reverse transcription­quantitative PCR were used to detect the expression level of CDCA5 in human normal mammary cells and human breast cancer cell lines. To determine its function in MDA­MB­231 cells, CDCA5 was silenced in MDA­MB­231 cells by transient short hairpin RNA transfection. Cell Counting Kit­8 and clonogenicity assays were used to evaluate cell proliferation. Wound healing and Transwell assays were used to detect cell invasion and migration. Western blot analysis was used to detect the protein expressions of Ki67 and PCNA associated with proliferation, MMP2 and MMP9 associated with migration. CDCA5 was found to be markedly increased in breast cancer cell lines. CDCA5 knockdown was able to suppress cell proliferation, invasion and migration. CDCA5 inhibition downregulated PDS5 cohesin­associated factor A (PDS5A) expression in breast cancer cells. PDS5A overexpression was found to reverse the effect of CDCA5 inhibition on breast cancer cell proliferation and migration. CDCA5 knockdown was shown to suppress the malignant progression of breast cancer cells by regulating PDS5A. The present findings may provide new potential targets for breast cancer therapy.

Elaiophylin triggers paraptosis and preferentially kills ovarian cancer drug-resistant cells by inducing MAPK hyperactivation.

Finely tuned mitogen-activated protein kinase (MAPK) signaling is important for cancer cell survival. Perturbations that push cells out of the MAPK fitness zone result in cell death. Previously, in a screen of the North China Pharmaceutical Group Corporation's pure compound library of microbial origin, we identified elaiophylin as an autophagy inhibitor. Here, we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum (ER) stress, ER-derived cytoplasmic vacuolization, and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer cells. Genome-wide CRISPR/Cas9 knockout library screening identified SHP2, an upstream intermediary of the MAPK pathway, as a critical target in elaiophylin-induced paraptosis. The cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) assay further confirmed the direct binding between the SHP2 and elaiophylin. Inhibition of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy inhibition. Interestingly, elaiophylin markedly increased the already-elevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK levels. Elaiophylin overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum, taxane, or PARPi, suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.

[Study on pharmacokinetics of puerarin in rats following different methods of administration of Tongqiao Sanyu prescription].

OBJECTIVE: To study pharmacokinetic of puerarin in rats following different methods of administration of Tongqiao Sanyu prescription. METHOD: Tongqiao Sanyu prescription was administered to rats by caudal vein injection, nasal administration and oral administration. Plasma samples were extracted with methanol and the plasma concentration of puerarin was analyzed by RP-HPLC. The pharmacokinetic parameters and bioavailability were calculated with Kinetica software. RESULT: The main pharmacokinetic parameters were as follows: AUC(0-infinity) of caudal vein injection was (787.99 +/- 70.44) mg x min x L(-1); AUC(0-infinity) of nasal administration was (376.56 +/- 93.93) mg x min x L(-1); AUC(0-infinity) and oral administration (The dose was decuple higher than that of caudal vein injection and nasal administration) was (491.18 +/- 110.64) mg x min x L(-1). The absolute bioavailability of puerarin was 47.78% by nasal administration and 6.23% by oral administration. CONCLUSION: The bioavailability of nasal administration is higher than oral administration significantly, this result can provide some scientific foundantion for the method of administration and the reform of dosage form of Tongqiao Sanyu prescription.

Simultaneous determination of five amino acid neurotransmitters in rat and porcine blood and brain by two-dimensional liquid chromatography.

A method for the simultaneous determination of aspartic acid (Asp), glutamic acid (Glu), glycine (Gly), taurine (Tau) and gamma-aminobutyric acid (GABA) in animal blood and brain by two-dimensional liquid chromatography (2D-LC) combined with ultraviolet detection was established for the first time. First, the amino acid neurotransmitters (AANTs) were labeled on the corresponding fluorescent derivatives with 4-fluoro-7-nitrobenzofurazan (NBD-F), enriched on the extraction column and automatically transferred to the analytical column to achieve on-line extraction and complete separation of the target components. This method exhibited good selectivity, and the correlation coefficients for the analyte calibration curves of were > 0.99. The intra- and inter-day precisions were ≤ 16.03, and the accuracies were in the range of 70.59-116.20%. The system realizes the rapid detection and stability quantification of the five AANTs, which proves that the alternative dilution method is feasible. The results show that the system has high loading capacity, excellent resolution, and good peak shape and is not affected by other endogenous substances. Moreover, the developed method has been successfully applied to the analysis of biological samples in the blood and whole brain of rats and pigs. The content of AANTs in the hippocampus and cortex of rats was higher than that in those of pigs. This method is expected to provide applicability for the determination of AANTs in pharmacological, pharmaceutical and clinical research in nervous science.