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Complex mass transfer processes are highly involved in the performance of counter-current chromatography (CCC), so profound exploration should be conducted to improve the overall performance. To more accurately estimate the interphase mass transfer efficiency in the elution process, this study proposes an incomplete mixed cell model by linking layering-mixing-layering behavior and wave-like mixing. With the model, we proposed a fast estimation algorithm for interphase mass transfer ratio (IMTR), which can independently reflect the magnitude of the interphase mass transfer efficiency. The experimental results show that the IMTR of all samples was relatively small, with an average value of not >10 % under different operating conditions. This indicates that the low column efficiency of CCC may be mainly due to the low efficiency of interphase mass transfer. In addition, by analyzing the influencing factors of IMTR, it is found that IMTR is positively correlated with the number of theoretical plates and the retention of stationary phase (S f ), but negatively correlated with the number of incomplete mixing cells (n). Therefore, in the study of column efficiency optimization, we recommend that the distribution ratio, S f , and n should remain unchanged in control experiments to ensure that IMTR directly reflects the effect on interphase mass transfer efficiency. This study further completes the evaluation index of the CCC column efficiency, revealing the underlying mechanisms of IMTR on column efficiency and providing a theoretical foundation for future research on high-efficiency CCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Chlorfenapyr is a novel broad-spectrum insecticide derived from natural pyrrole derivatives produced by Streptomyces spp. It acts as a pro-insecticide and is metabolically converted to the active metabolite, tralopyril. Chlorfenapyr poisoning is known for its delayed neurological symptoms and high mortality. Unfortunately, information on the toxicokinetics, metabolism and tissue distribution of chlorfenapyr and tralopyril is still lacking. In this study, the metabolic profile, toxicokinetics and tissue distribution of chlorfenapyr and tralopyril after oral administration at a toxic dose in mice were investigated. Twenty metabolites were identified in plasma, urine and feces, which were mainly formed by dealkylation, oxidative dechlorination and reductive dechlorination. Toxicokinetic results showed that chlorfenapyr was rapidly converted to tralopyril after administration, and the in vivo half-life (t 1/2 ), area under the curve (AUC) and peak concentration (C max ) values of tralopyril were significantly higher than those of chlorfenapyr (P < 0.05). Tissue distribution experiments confirmed that the metabolite tralopyril had a longer half-life, a lower clearance and a wide distribution in different organs and tissues compared to chlorfenapyr. It was also able to cross the blood-brain barrier, suggesting a potential association with brain lesions. In addition, a sensitive and rapid LC-MS/MS analytical method was established for the detection of chlorfenapyr and tralopyril. In conclusion, this study provided valuable metabolic, toxicokinetic and tissue distribution information, contributing to future risk assessment and forensic identification in cases of chlorfenapyr poisoning. We recommend considering the assessment of tralopyril levels, which may be of greater therapeutic importance in the management of chlorfenapyr poisoning., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In counter-current chromatography (CCC), linear scale-up is an ideal amplification strategy. However, when transferring from analytical to predictable preparative processes with high throughput, linear scale-up would be challenging due to limitations imposed by differences in instrument parameters, such as gravitational forces, tubing cross-section area, tubing length, column volume and flow rate. Some effective scale-up strategies have been studied for different instrument parameters, but so far, these scale-up works have only been tested on standard circular (SC) tubing. The previous research of our group found that rectangular horizontal (RH) tubing can double the separation efficiency compared with conventional SC tubing, and has industrial production potential. This paper used the separation of tilianin from Dracocephalum moldavica L. as an example to demonstrate how to scale up the optimized process from analytical SC tubing to preparative RH tubing. After systematic optimization of solvent systems, sample concentration and flow rate on the analytical CCC, the optimized parameters obtained were successfully transferred to the preparative CCC. The results showed that a crude sample of 2.07 g was successfully separated using a solvent system of n-hexane - ethyl acetate - ethanol - water (1:4:1:5, v/v/v/v) in reversed phase mode, and the three consecutive separations produced a total of 380 mg tilianin in 75 min with high purities of 98.3%, as analyzed by HPLC. The total throughput achieved from the analytical to semi-preparative scale was improved by 138 times (from 12 mg/h to 1.66 g/h), while the column volume was increased by only 46.5 times (from 15.5 mL to 720 mL). This is the successful application of CCC for the separation and purification of tilianin. Given that SC tubing is the traditional configuration for CCC columns, this study is a necessary step to prove the applicability of RH tubing columns for routine use and potential large-scale industrial applications., Competing Interests: Declaration of competing interest All authors declare that No conflict of interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Counter-current chromatography (CCC) is a widely used liquid-liquid separation technique. Much work has been performed to improve the retention of stationary phases and throughput. In previous research, high aspect ratio rectangular horizontal (RH) tubing has been proven to be able to improve resolution and throughput in comparison with standard circular (SC) tubing. However, those modifications and improvements of tubing shapes have only been tested on analytical tubing thus far. This study aims to verify whether RH tubing could achieve similar high stationary phase retention (Sf) and throughput on a semi-preparative CCC apparatus. First, a lighter and larger volume semi-preparative bobbin with thin-wall RH tubing was successfully manufactured. Then the Sf of this bobbin was tested with n-hexane-ethyl acetate-methanol-water (HEMWat) and dichloromethane-methanol-water (DMW) solvent systems, and its maximum throughput was explored with the mixture of Magnolia officinalis Rehd. Et Wils. The results show that the thin-wall RH tubing bobbin can retain high Sf for these solvent systems, even at a relatively high mobile phase flow rate, which is consistent with the analytical bobbin results. The throughput test demonstrates that 2.12 × throughput can be obtained with the RH tubing column bobbin compared to the conventional SC tubing column bobbin without changing the outside dimensions of the bobbin. The present study is a necessary step for the application of the RH tubing bobbin from a laboratory analytical scale to preparative industrial scale., Competing Interests: Declaration of Competing Interest All authors declare that No conflict of interest exists., (Copyright © 2021 Elsevier B.V. All rights reserved.)

At present, there is no specific anti-metastasis drug in HCC treatment. Drugs used for primary HCC tumors and tumor metastasis are very similar, among which cytotoxic drugs are prevalent, such as cisplatin, doxorubicin and 5-FU. The EGFR pathway plays an important role in promoting hepatocellular carcinoma (HCC) metastasis. Hence, development of non-toxic anti-metastasis drugs, such as EGFR or downstream pathways inhibitors, is of great importance. In our present study, we found non-toxic dose of liposomal honokiol (LH) could inhibit the HCC metastasis by destabilizing EGFR and inhibiting the downstream pathways. Non-toxic dose of LH significantly inhibited the motility, migration and lamellipodia formation of HepG2 cells in vitro and decreased extravasation of HepG2 cells in a novel metastasis model of transgenic zebrafish. In two lung metastasis models (HepG2 and B16F10) and a spontaneous metastasis model of HepG2 cells, LH remarkably inhibited pulmonary metastasis and regional lymph nodes metastasis without obvious toxicity. Further study showed that destabilizing EGFR and inhibiting the downstream pathways were the main mechanisms of non-toxic dose of LH on metastasis inhibition. Our results provide the preclinical rationale and the underlying mechanisms of LH to suppress HCC metastasis, implicating LH as a potential therapeutic agent to block HCC metastasis without severe side effects.

The potential antidiabetic activity of ethyl acetate extract of the leaves of Lagerstroemia speciosa (LSL) was investigated by alpha-amylase and alpha-glucosidase inhibition assay. Six pentacyclic triterpenes (oleanolic acid, arjunolic acid, asiatic acid, maslinic acid, corosolic acid and 23-hydroxyursolic acid) were isolated from LSL. Their structures were determined by spectroscopic analysis and their alpha-glycosidase and alpha-amylase inhibitory activities were investigated. They exhibited no or weak inhibitory activity against alpha-amylase and middle alpha-glucosidase inhibitory activities. Corosolic acid, which shows best bioactivity against alpha-glucosidase (IC(50) = 3.53 microg/mL), contributes most to the alpha-glucosidase inhibitory activity of EtOAc extract. The kinetics of inhibition of corosolic acid was also discussed. Results from this study might provide the scientific evidence for LSL for the treatment of diabetes in traditional medicine.

Objective: To explore the efficacy of PSC 833 on multidrug resistance (MDR) reversal and its mechanism., Methods: Human erythroleukemic cell line K562 and its doxorubicin-resistant counterpart K562/A02 were used in the study. Cytotoxicity was assessed by MTT assay, P-gp expression by direct immunofluorescence and mdr1 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR) with beta-actin as internal control. Intracellular DNR retention was measured with flow cytometry., Results: K562/A02 cells displayed high levels of mdr1 mRNA and P-glycoprotein and reduced DNR retention compared to their parental K562 cells. 1 micromol/L of PSC 833 had no effect on the levels of mdr1 mRNA and P-gp expression in K562/A02 cells (P > 0.05). PSC 833 conferred a dose-dependent increase on chemosensitivity of K562/A02 to DNR, and its effect was at least 3-fold more potent than that of CsA or Ver. PSC 833 could increase DNR retention in K562/A02 cells. A 100.9% restoration of intracellular DNR retention of the level of K562 cells was gained by PSC 833 at 1.0 micromol/L in K562/A02 cells, whereas only a 86.9% restoration of DNR retention was obtained by CsA at 10 micromol/L in the K562/A02 cells. No effect on DNR sensitivity and retention was found in K562 cells (P > 0.05)., Conclusion: PSC 833 is at least 3 approximately 10 fold more potent than CsA or Ver with respect to MDR reversing activity, and it may function by inhibiting the function of P-gp and not reducing the levels of mdr1 mRNA and P-gp directly.