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In this study, functionalized carbon dots were synthesized in one step from L-histidine and imidazolyl ionic liquids using an ionic liquid-assisted microwave method as green corrosion inhibitors for steel in a 1 M HCl solution. Different ionic liquid anions (CF 3 COO- and HSO 4 -) were introduced in the preparation of the carbon dots, and their microstructures and surface properties were characterized. Notably, the corrosion inhibition efficiency of the prepared CDs (assisted by CF 3 COO-) reached 94.2% at 5 mg‧dm−3. The corrosion inhibition behavior of CDs on mild steel in 1 M HCl was investigated through DFT calculations. Our investigation revealed that the anions of the selected ionic liquids have a certain influence on the structure of the carbon dots, which correlates with the performance of the carbon dot corrosion inhibitor. Therefore, this study provides guidance for the preparation of functionalized carbon dot corrosion inhibitors using a one-step microwave method and the selection of ionic liquids (as solvents, modifiers, and mediums for microwave conversion). [Display omitted] • Carbon dot corrosion inhibitors modified by ionic liquids are synthesized by the one-step microwave method. • The ionic liquid-derived microwave-assisted method has the advantages of time-saving and energy-saving. • The link between the structures of ionic liquids, carbon dots, and their corrosion inhibition properties is discussed. • The carbon dots show good corrosion inhibition efficiency (94.2%) at an ultra-low concentration (5 ppm). • The adsorption of carbon dots on the steel surface was studied by Density Functional Theory. [ABSTRACT FROM AUTHOR]

Troxerutin, a semi-synthetic derivative of the natural bioflavanoid rutin, has been reported to possess many beneficial effects in human bodies, such as vasoprotection, immune support, anti-inflammation and anti-aging. However, the effects of troxerutin on genome-wide transcription in blood cells are still unknown. In order to find out effects of troxerutin on gene transcription, a high-throughput RNA sequencing was employed to analysis differential gene expression in blood cells consisting of leucocytes, erythrocytes and platelets isolated from the mice received subcutaneous injection of troxerutin. Transcriptome analysis demonstrated that the expression of only fifteen genes was significantly changed by the treatment with troxerutin, among which 5 genes were up-regulated and 10 genes were down-regulated. Bioinformatic analysis of the fifteen differentially expressed genes was made by utilizing the Gene Ontology (GO), and the differential expression induced by troxerutin was further evaluated by real-time quantitative PCR (Q-PCR). [ABSTRACT FROM AUTHOR]

The content of styrene units in nonhydrogenated and hydrogenated styrene-butadiene-styrene and styrene-isoprene-styrene triblock copolymers significantly influences product performance. A size exclusion chromatography method was developed to determine the average styrene content of triblock copolymers blended with tackifier in adhesives. A complete separation of the triblock copolymer from the other additives was realized with size exclusion chromatography. The peak area ratio of the UV and refraction index signals of the copolymers at the same effective elution volume was correlated to the average styrene unit content using nuclear magnetic resonance spectroscopy with commercial copolymers as standards. The obtained calibration curves showed good linearity for both the hydrogenated and nonhydrogenated styrene-butadiene-styrene and styrene-isoprene-styrene triblock copolymers ( r = 0.974 for styrene contents of 19.3-46.3% for nonhydrogenated ones and r = 0.970 for the styrene contents of 23-58.2% for hydrogenated ones). For copolymer blends, the developed method provided more accurate average styrene unit contents than nuclear magnetic resonance spectroscopy provided. These results were validated using two known copolymer blends consisting of either styrene-isoprene-styrene or hydrogenated styrene-butadiene-styrene and a hydrocarbon tackifying resin as well as an unknown adhesive with styrene-butadiene-styrene and an aromatic tackifying resin. The methodology can be readily applied to styrene-containing polymers in blends such as poly(acrylonitrile-butadiene styrene). [ABSTRACT FROM AUTHOR]

Metal-free blue light-mediated [2,3]-sigmatropic rearrangement reactions of tosylhydrazones and sulfides are reported herein. This strategy shows great enhancement compared to the traditional methods because of stable starting materials and mild reaction conditions. In this report, we have developed the Doyle-Kirmse reaction and Sommelet-Hauser reaction with simple operation, high yields and broad substrate adaptability. [Display omitted] Metal-free blue light-mediated [2,3]-sigmatropic rearrangement reactions of tosylhydrazones and sulfides are reported herein. This strategy shows great enhancement compared to the traditional methods because of stable starting materials and mild reaction conditions. In this report, we have developed the Doyle-Kirmse reaction and Sommelet-Hauser reaction with simple operation, high yields and broad substrate adaptability. [ABSTRACT FROM AUTHOR]

Abstract: A series of new organotin carboxylates have been synthesized by reactions of trans(cis)-1,4-cyclohexanedicarboxylic acid with triorganotin chloride and diorganotin dichloride. All the complexes were characterized by elemental analysis, IR, 1H NMR, 13C NMR, 119Sn NMR spectroscopy; furthermore, complexes 1, 3, 5, 8 and 9 were characterized by X-ray diffraction analyses. The structural analyses show that complex 1 possesses a monomer structure; complex 5 possesses a 1D zigzag chain structure; both the complexes 3 and 8 have 2D network structures and complex 9 has a tetratin 36-membered macrocyclic structure. [Copyright &y& Elsevier]

Abstract: A linear sweep stripping voltammetric (LSSV) method has been researched and developed for simultaneous quantitative determination of mixtures of three antibiotic drugs, ofloxacin, norfloxacin and ciprofloxacin. It relies on reductive reaction of the antibiotics at a mercury electrode in a Britton–Robinson buffer (pH 3.78). The voltammograms of these three compounds overlap strongly, and show non-linear character. Thus, it is difficult to analyse the compounds individually in their mixtures. In this work, chemometrics methods such as classical least squares (CLS), principal component regression (PCR), partial least squares (PLS) and radial basis function-artificial neural networks (RBF-ANN) were applied for the simultaneous determination of these compounds. The prediction performance of the calibration models constructed on the basis of these methods was compared. It was shown that satisfactory quantitative results were obtained with the use of the RBF-ANN calibration model relative prediction error (RPET) of 8.1% and an average recovery of 101%. This method is able to accommodate non-linear data quite well. The proposed analytical method based on LSSV was applied for the analysis of ofloxacin, norfloxacin and ciprofloxacin antibiotics in bird feedstuffs and their spiked samples, as well as in eye drops with satisfactory results. [Copyright &y& Elsevier]

A voltammetric method, aided by chemometrics, was developed for the simultaneous determination of paracetamol and phenobarbital in pharmaceuticals. Both of these analytes gave well-defined oxidation peaks in the Britton–Robinson buffer(pH 5.72) when analyzed by differential pulse-stripping voltammetry(DPSV) at a glassy carbon electrode. The experimental conditions were optimized: 200 mV—deposition potential, 160 s—deposition time, 4 mV—increment potential, 50 mV—amplitude, and 60 ms—pulse width. Under these selected conditions, the oxidation current had a linear relationship with concentration of paracetamol[ranges: 0.09–0.93 mg l−1(r2 = 0.999) and 0.9–11.7 mg l−1(r2 = 0.999)], and phenobarbital[1.0–22.0 mg l−1(r2 = 0.999)]. Due to the overlapping voltammograms from the two analytes, two chemometrics methods, partial least squares(PLS), and principal component regression(PCR), were used for building calibration models from voltammograms of mixtures. These models were applied for prediction of the analytes from unknown samples. It was found that the two chemometrics methods gave good results for analysis of mixtures of these two compounds. The proposed method was verified by an established HPLC method, and its practical application was demonstrated with the determination of paracetamol and phenobarbital in several commercial tablets with satisfactory results. [ABSTRACT FROM AUTHOR]

Driver intention prediction allows drivers to perceive possible dangers in the fastest time and has become one of the most important research topics in the field of self-driving in recent years. In this study, we propose a driver intention prediction method based on multi-dimensional cross-modality information interaction. First, an efficient video recognition network is designed to extract channel-temporal features of in-side (driver) and out-side (road) videos, respectively, in which we design a cross-modality channel-spatial weight mechanism to achieve information interaction between the two feature extraction networks corresponding, respectively, to the two modalities, and we also introduce a contrastive learning module by which we force the two feature extraction networks to enhance structural knowledge interaction. Then, the obtained representations of in- and outside videos are fused using a ResLayer-based module to get a preliminary prediction which is then corrected by incorporating the GPS information to obtain a final decision. Besides, we employ a multi-task framework to train the entire network. We validate the proposed method on the public dataset Brain4Car, and the results show that the proposed method achieves competitive results in accuracy while balancing performance and computation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ecosystem services are benefits humans obtain from ecological systems. • Temporal and spatial dynamics and drivers of supply–demand relationships studied. • Multidisciplinary and multi-method approach using multi-data sources. • Supply/demand of eight ESs in the DJKR area have clear spatiotemporal variability. • Spatial guidance and decision-making basis for ES optimization. The supply–demand, spatial matching, trade-offs, and synergies of ecosystem services (ESs) are important foundations for sustainable environmental management. The Danjiangkou Reservoir area (DJKR) is an important water source for the South-to-North Water Diversion Middle Route Project in China. Spatiotemporal dynamics of supply and demand for eight ESs between 2000 and 2020 were studied using the food–energy method, InVEST model, recreation opportunity spectrum, supply–demand matching relationship, and geographically weighted regression. From 2000 to 2020, supply and demand of the eight ESs displayed clear spatiotemporal variability; geographic detector analysis showed that land-use types were strong determinants of supply, with the interactions between each factor stronger than those between single factors. Demand for ESs was limited by natural–social factors. The supply–demand ratios of each indicator varied spatially (at regional, county, and sub-watershed scales) and temporally. Similarly, trade-off synergistic relationships also changed at all three spatial scales. Spatial control areas (levels I–IV) were delineated, and corresponding management programs were proposed. The results of this study strengthen our understanding of the spatiotemporal variation and driving factors in ES supply–demand, and provide technical and theoretical support for spatial management policies for ESs in the DJKR. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Benzothiadiazine‐1,1‐dioxide scaffold is bioactive framework with wild utility and applications. Synthesis of benzothiadiazine‐fused isoquinoline derivatives and spiro benzothiadiazine derivatives through transition metal‐catalyzed C—H activation/annulation was reported. 3‐Phenyl‐2H‐benzothiadiazine‐1,1‐dioxide was used as the reaction substrate, and vinylene carbonate and 4‐diazopyrazolone were used as the coupling reagents, respectively. This strategy provides straightforward access to complex N‐heterocycles in a highly efficient and simple manner. [ABSTRACT FROM AUTHOR]

Oxidative stress is one of the elements causing aging and related diseases. Inhibiting Nrf2 activity or increasing oxidative pressure can replicate the deficits of premature aging. SIRT6 is one of the few proteins that can regulate both life span and aging. Deletion of SIRT6 in human cells impairs the antioxidant capacity of cells, which results in the accumulation of intracellular reactive oxygen species and DNA oxidation products. Characterization of the binding of Nrf2 with SIRT6 is critical for understanding the modulation of Nrf2-correlated cell activities by SIRT6. The yeast two-hybrid experiments showed that the binding of Nrf2 with SIRT6 is mediated by Neh1 and Neh3 domains. The elimination of the Neh1 and Neh3 domains decreased the binding stability and free energy, according to the molecular dynamic analysis. The roles of theses domains in mediating the binding were confirmed by co-immunoprecipitation. In cells transfected with the small interfering RNA (siRNA) targeting the Nrf2 Neh1 domain and plasmids overexpressing domain-mutant Nrf2, it was discovered that Nrf2 lost its activity to stimulate the transcription of antioxidant genes in the absence of Neh1 and Neh3 domains. • Deletion of Neh1 or Neh3 domains decreased the binding free energy of Nrf2 to SIRT6. • The binding of Nrf2 to SIRT6 is mediated by Neh3 and especially Neh1 domains. • Neh1 and Neh3 domains are also required for Nrf2-dependent expression of anti-oxidant genes. [ABSTRACT FROM AUTHOR]

Abstract Keap1 is deemed as a suppressor of Nrf2 in cytoplasm by sequestrating Nrf2 to proteolysis as an adapter of the Cul3-Rbx1 E3 ubiquitin ligase complex. In the study, it was proposed that post-translational modification might affect the interaction between Nrf2 and Keap1, and the profiles of the phosphorylation of amino acid residues of Keap1 and its effects on the binding of Keap1 to Nrf2 was investigated. A mass spectrometry analysis revealed that S53 and S293 were phosphorylated upon an oxidative stress. Using Keap1 proteins with amino acid residues mutated to glutamate to simulate the introduction of a negative charge by phosphorylation, it was found that a potential phosphorylation of S53 affected Keap1-Nrf2 binding in the pull-down assay, and induced nuclear translocation of Nrf2 in the electrophoretic mobility shift assay. Sequence homology analysis showed that S53 was highly conserved. Structural modeling around BTB domain of wild type and S53E-mutant Keap1 showed that the negative charge introduced by S53E mutation generates a salt bridge between E53 and ionized guanidine group of Arg50. Real-time qRT-PCR for transcription levels of antioxidant genes that are modulated by Nrf2 further proved the effects of the potential phosphorylation of S53 under an oxidative stress condition. In summary, S53 is a potential phosphorylation site of Keap1, and the phosphorylation could enhance the antioxidative capacity of cells in response to an oxidative stress. Highlights • S53 is a potential phosphorylation site of Keap1, influencing stress response in cells mediated by Nrf2, which is a transcription factor. [ABSTRACT FROM AUTHOR]

This paper reports a single-layered microfluidic device for studying the interaction of cancer cells and fibroblasts in an oxygen gradient. This gradient can be established from 1.9% to 18.8% using a spatially confined oxygen scavenging chemical reaction. Due to the spatial design of the chip, only cancer cells can sustain low oxygen conditions when co-cultured with fibroblasts in the adjacent channels, simulating the cell–cell interactions of the hypoxic cancer cells and the surrounding fibroblasts in tumor microenvironment in vivo. Moreover, a cell migration assay is performed on the chip for studying the tumor invasion ability. The results show that the migration speed of B16 cells is increased by hypoxia and the co-culture with L929 cells. In addition, we use ELISA to quantify the migration-related cytokines transforming growth factor-β1 (TGF-β1) in the microfluidic system. Our results confirm interaction between cancer cells and fibroblasts. This microfluidic device provides new insight for the investigation of tumor microenvironment and cell interactions. [ABSTRACT FROM AUTHOR]

• A semi-analytical model with a new layout of 14 flexible tubes is presented. • Three sets of experimental data are used for modeling verification. • Accuracy and efficiency of models with 1, 7, and 14 tubes are compared. • Interactions between tubes and cross-flow are analyzed in the time and spatial domain. • Parametric study about three empirical inputs of the models is carried out. The semi-analytical model (a.k.a. the tube-in-channel model) needs less empirical inputs and considers interactions between tube movements and cross-flow variables, and is well used in fluidelastic instability (FEI) threshold prediction of tube bundles. However, despite numerous flexible tubes in engineering practice, tube-in-channel models with more than 7 tubes are not yet studied. In this paper, a new tube-in-channel model with a layout of 14 flexible tubes, rather than the reported 1, 5, or 7 tube(s), is established and used for FEI threshold prediction of rotated triangular tube bundles in two-phase cross-flow. Five sets of experimental data are used for verifying this model, of which the accuracy and efficiency are compared with those of tube-in-channel models with 1 and 7 tube(s). Influences of the attachment angle, the separation angle, and the time-delay parameter on performances of these three models are also investigated. Since its numerical predictions agree well with the experiments, the present 14-tubes model shows potential applications in steam generator design. [ABSTRACT FROM AUTHOR]

Despite progress in the application of checkpoint immunotherapy against various tumors, attempts to utilize immune checkpoint blockade (ICB) agents in triple negative breast cancer (TNBC) have yielded limited clinical benefits. The low overall response rate of checkpoint immunotherapy in TNBC may be attributed to the immunosuppressive tumor microenvironment (TME). In this study, we investigated the role of mitogen-associated kinase TTK in reprogramming immune microenvironment in TNBC. Notably, TTK inhibition by BAY-1217389 induced DNA damage and the formation of micronuclei containing dsDNA in the cytosol, resulting in elicition of STING signal pathway and promoted antitumor immunity via the infiltration and activation of CD8+ T cells. Moreover, TTK inhibition also upregulated the expression of PD-L1, demonstrating a synergistic effect with anti-PD1 therapy in 4T1 tumor-bearing mice. Taken together, TTK inhibition facilitated anti-tumor immunity mediated by T cells and enhanced sensitivity to PD-1 blockade, providing a rationale for the combining TTK inhibitors with immune checkpoint blockade in clinical trials. • Breast cancer, especially triple negative breast cancer, shows higher TTK expression than normal breast tissue. • Inhibition of TTK generates cytosolic dsDNA and activates STING signaling in TNBC cells. • TTK inhibitor suppresses 4T1 tumor growth dependent on CD8+ T cells and modulates tumor immune microenvironment. • Inhibition of TTK synergistically enhances the effectiveness of anti-PD1 therapy in subcutaneous 4T1 tumor model. [ABSTRACT FROM AUTHOR]

The fermentation product of Cordyceps sinensis mycelium Cs‐4 was commonly used as alternative substitutes of natural C. sinensis. Massoia lactone is the dominant component in the volatile oil of Cs‐4 mycelium. In this research, we present a high performance liquid chromatography (HPLC) method for the quantitation of massoia lactone in Cs‐4 mycelium. The high and stable contents of massoia lactone with values of 2.98–3.77 mg/g, indicated that massoia lactone could be considered as a marker for the quality assessment of this product. The results of MTT and CCK‐8 assay showed that Cs‐4 mycelium volatiles exhibited cytotoxicity against eight malignant tumor cells (IC50 = 6.0–49.8 μg/ml) in comparison to the anticancer drug 5‐fluorouracil (IC50 = 17.0–425.3 μg/ml), and massoia lactone might be the chemical basis for the anticancer effects of Cs‐4 mycelium. Compared to the commercial drugs paclitaxel and docetaxel (IC50 = 253–1973 μg/ml), the Cs‐4 mycelium volatiles and massoia lactone were discovered to possess inhibitory to taxol‐resistant cell lines (IC50 = 1.5–8.6 μg/ml). Practical applications: Considering that there is still a lack of marker components distinctive to Cs‐4 mycelium, the HPLC method represents a useful tool for the quality evaluation of Cs‐4 mycelium. Moreover, the volatile oil of Cs‐4 mycelium and massoia lactone have prominent anticancer property in vitro. It gives a clue that Cs‐4 mycelium, the volatile oil and massoia lactone could be potentially employed in the food and medical industries for its anticancer applications. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with synaptic dysfunction, pathological accumulation of β‐amyloid peptide 1‐42 (Aβ1‐42), and neuronal loss. The self‐association of Aβ1‐42 monomers (Aβ‐M) into soluble oligomers seems to be crucial for the development of neurotoxicity. Previous publications have shown that Aβ oligomers and dimers might play key roles in inducing AD. The role of Aβ‐M was rarely investigated and still unclear in AD. To understand the effects of Aβ‐M on neurons and other cell types in the brain could be the key to understand its function. In our study, we found that Aβ‐M expression slowly induced cell apoptosis within 48 hours after transfection, β2 adrenergic receptor (β2AR) interacted with Aβ‐M in the pull‐down and the yeast two‐hybrid assays, and Aβ‐M played a major role in inducing phosphorylation of Tau at Ser‐214, c‐Jun N‐terminal kinase (JNK) at Thr‐183/Tyr‐185, p70 ribosomal protein S6 kinase (p70S6K) at Thr‐389. We also discovered that β2AR, G protein‐coupled receptor kinase 2 (GRK2), and protein kinase A (PKA) mediated the phosphorylation of Tau and JNK. Aβ‐M induced phosphorylation of Tau at Ser‐214 through both β2AR‐cAMP/PKA‐JNK and β2AR‐GRK signaling pathways. Mitogen‐activated protein kinase kinase (MEK) mediated the phosphorylation of p70S6K induced by Aβ‐M. [ABSTRACT FROM AUTHOR]

Forsythiaside A is the major component of Forsythia suspensa. This study investigated the degradation mechanism of forsythiaside A. Eight degraded components including forsythiaside I, forsythiaside H, forsythiaside E, caffeic acid, suspensaside A, β‐hydroxy forsythiaside I, β‐hydroxy forsythiaside H, and β‐hydroxy forsythiaside A were identified by using ultra‐high performance liquid chromatography quadrupole time‐of‐flight mass spectrometry. Then, the quantitative analysis of multi‐components by a single‐marker was performed with ultra‐high performance liquid chromatography to simultaneously determine forsythiaside A, forsythiaside H, and forsythiaside I in Forsythia suspensa preparations. The result showed good linear relationships within 2.871–287.1, 0.231–23.1, and 0.983–98.3 μg/mL (r > 0.9998), with average recoveries of 97.7, 95.7, and 95.8% and relative standard deviations of 1.4, 2.4, and 1.8%, respectively. Using forsythiaside A as an internal reference, the relative retention values of forsythiaside H and forsythiaside I to forsythiaside A were calculated to be 0.89 and 0.61, respectively, and the relative correction factors were 0.816 and 0.799, respectively. The method for quantitative analysis of multi‐components by a single‐marker was applied to evaluate the overall quality of forsythia preparations. There was no significant difference in the measurement results of the method developed and the method of external standard. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells (HSCs), a major component of the tumor microenvironment in liver cancer, play important roles in cancer progression as well as drug resistance. Here, we presented a microchannel plate-based co-culture model that integrated Hepa1–6 tumor spheroids with JS-1 stellate cells in three-dimensional (3D) concave microwells to mimic the in vivo tumor microenvironment by recapitulating epithelial–mesenchymal transition and chemoresistance. The expression of epithelial–mesenchymal transition (EMT)-related markers and factors was analyzed using immunofluorescent staining and the changes in viability following exposure to different concentrations of paclitaxel were measured. Cell spheroids formed 3D tumor spheroids within 3 days. Culture conditions were optimized for Hepa1–6 cells and JS-1 cells, and their appropriate interactions were confirmed by reciprocal activation. JS-1 under co-culture showed a change in cellular morphology and an increased expression of α-SMA. The expression of EMT-related markers, such as vimentin and TGF-β1, was higher in the co-cultured Hepa1–6 spheroids compared to that in mono-cultured spheroids. Following paclitaxel exposure, JS-1 cells showed significant changes in survival under both mono- and co-culture conditions, while Hepa1–6 presented negligible changes. The proposed microfluidic platform makes it possible to observe the positioned three-dimensional cell spheroids, which would be extensively used not only for well-organized spheroid creation, but also for better quantitative and qualitative understanding of the cell–cell interaction effect. [ABSTRACT FROM AUTHOR]

Highlights • An original concentration gradient generator for investigating drug synergy. • Generating spatially and temporally stable concentration gradients with a high degree of control over shapes of gradients. • Able to generate gradients of three or more substances with high flexibility in structure modification. • Assaying the sensitivities of cells to single and combined anti-cancer drugs in parallel with ease in this microfluidic chip. Abstract In this paper we aimed to figure out an effective platform for generating gradients of three or more substances and designed an original microfluidic network with circular shape controlling diffusive mixing of fluids. The generated gradients were calculated by a theoretical treatment using a CFD model and verified in the fluorescence experiments, certifying that they maintained a spatially and temporally stable linearity under the flow rate of 2 μL/min. Finally, we applied the platform for generating gradients on study of the drug synergism. 5-fluorouracil and tanshinone IIA (Tan IIA) were used for biological applicability via stimulation of single or multidrug combination on A549 cells. Consistent with the traditional MTT assays, both of the two drugs inhibited the cancer cell growth effectively and the IC 50 values of 5-fluorouracil and Tan IIA were 20.37 and 44.78 mg/L, while their combination was superior. This microfluidic network is a simple and reliable platform as a gradient generator for investigating the possible combination of multiple drug candidates and their optimum dosage. [ABSTRACT FROM AUTHOR]

• Pharmacodynamics and metabolomics deciphered therapeutic mechanism of ZSXBGZD against MI/R. • ZSXBGZD attenuated oxidative stress and mitochondrial dysfunction to avoid cardiomyocyte injury. • Cell polar metabolites revealed the effect of ZSXBGZD on energy and amino metabolism. • HILIC and UPLC-Q-TOF-MS method was applied to insight polar metabolites related to H/R and potential mechanism of ZSXBGZD. Myocardial ischemia/reperfusion (MI/R) injury is a life-threatening syndrome with high morbidity and mortality. Zhishi-Xiebai-Guizhi Decoction (ZSXBGZD) is a classic traditional Chinese medicine formula, used to treat cardiovascular diseases for centuries. However, its underlying medicinal mechanism has not been clearly elucidated, which hinders its widespread application. Here, the curative effects and therapeutic mechanism of ZSXBGZD against MI/R were addressed based on an integration of pharmaceutical evaluation and cellular metabolomics. First, a hypoxia/reoxygenation (H/R) model in H9c2 cells was employed to resemble MI/R and multiple pharmacological indicators were performed to assess the efficacy of ZSXBGZD. The results showed that ZSXBGZD possessed exceptional ability in attenuating cardiomyocyte injury, concerning oxidative stress, mitochondrial dysfunction, energy acquisition and cell apoptosis. Furthermore, a cell metabolomics approach based on HILIC and UPLC-Q-TOF-MS coupled with multivariate analysis was conducted to explore the metabolic regulation of ZSXBGZD. 38 differential polar metabolites related to H/R were uncovered, and 34 of them were reversed to normal state after the treatment of ZSXBGZD, revealing the perturbations of energy metabolism and amino acid metabolism. Moreover, formula decomposition justified the combination of single herbs to form ZSXBZGD and confirmed the pivotal status of Allii Macrostemonis Bulbus and Trichosanthis Fructus. [ABSTRACT FROM AUTHOR]

Purpose: Adrenocorticotropic hormone (ACTH) is the only medicine for treating infantile spasms, however, it is catabolized rapidly. In order to make an ACTH derivative with prolonged effects, we prepared genetically engineered wild type (WT) and mutant ACTH candidates based on protease database analysis, and compared their stability and pharmacological effects. Methods: For analysis of stability, serum concentration of WT and mutant ACTH candidates were tested at different time after intravenous injection, and elimination curves were calculated to compare pharmacokinetic properties of WT and E5D-mutant ACTH. For comparison of their pharmacological effects, levels of glucocorticoids (GC) in the blood serum and secreted from cultured Y1 mouse adrenal cells were tested, and their effects on the signaling pathway mediating the expression of genes critical for GC synthesis were analyzed. The effects of ACTHs on transcription levels of the genes involved in GC synthesis were tested by qPCR. Results: The blood concentration of E5D ACTH is higher than the WT after injection, and E5D mutation increased the t and AUC of ACTH. Pharmacological experiments showed that the effects of E5D and Y2S mutant ACTH on the production of GC and the critical signal transduction were equivalent to those of WT. WT, E5D and Y2S ACTH also have similar effects on the transcriptional levels of the genes for GC synthesis, including STAR, P450-scc, 3β-HSD, and SF-1. Conclusion: The stability of E5D mutant ACTH is higher than WT ACTH. The pharmacological effects of E5D ACTH is equivalent to those of WT ACTH. [ABSTRACT FROM AUTHOR]

Panax ginseng has been applied in traditional Chinese medicine for over 2000 years. It is still one of the most popular herbs in recent decades. The prescribed ginseng-containing medicines consist of protopanaxadiol and protopanaxatriol ginsenosides, which are the major constituents of the herb. Minor ginsenosides at low levels in the herb, such as Rg3 and Rg5, have attracted more rising attention than the major ones. The existing approaches to prepare Rg3 and Rg5 usually rely on either steamed red ginseng as the source or chemical/enzymatic conversion of protopanaxadiol to the targets. It is still highly desirable to effectively achieve such minor components. In this paper, a method integrated extraction of protopanaxadiol and conversion of it to Rg3 and Rg5 has been proposed. Protopanaxadiol was extracted and simultaneously converted to Rg3 and Rg5 by d, l-tartaric acid. The targets were absorbed by resins on expanded bed adsorption chromatography and were then separated from other ginsenosides in different stages. Compared with conventional methods, the developed process has advantages in shortening time consumption and improving the conversion ratio of protopanaxadiol, which is promising in directly achieving Rg3 and Rg5 from P. ginseng. [ABSTRACT FROM AUTHOR]

St. John's wort has attracted particular attention because of its beneficial effects as an antidepressant, antiviral, and anticancer agent. A method for the combination of integrated expanded bed adsorption chromatography and countercurrent chromatography for the simultaneous extraction and purification of pseudohypericin and hypericin from the herb is presented in this paper. Firstly, the constituents were extracted and directly adsorbed by expanded bed adsorption chromatography under optimal conditions. The stepwise elution was then performed by expanded bed adsorption chromatography that enriched the targets with higher purities and recoveries compared to other methods. Secondly, the eluent fractions from expanded bed adsorption chromatography were further separated by two-step high-speed countercurrent chromatography. A two-step high-speed countercurrent chromatography method with a biphasic solvent system composed of n-hexane/ethyl acetate/methanol/water with a volume ratio of 1:2:1:2 was performed by stepwise changing the flow rate of the mobile phase. Consequently, 5.6 mg of pseudohypericin and 2.2 mg of hypericin with purities of 95.5 and 95.0%, respectively, were successfully obtained from 40 mg of crude sample. [ABSTRACT FROM AUTHOR]

Separation of polar alkaloids by countercurrent chromatography (CCC) is challengeable due to their close partition behaviors in solvent system. In this paper, a two-stage method for isolation of epiberberine, jatrorrhizine, palmatine, coptisine, and berberine from Rhizoma coptidis was presented. The first stage separation performed on CCC was based on the principle of reactive extraction. Trifluoroacetic acid was acted as a modulator to selectively react with alkaloids, which changed their partition coefficients in solvent system. Purified epiberberine and other partially separated targets were eluted by ammonium adjusted mobile phase. In the second stage, four alkaloids were purified in pH-zone-refining CCC mode. All the targets collected were over 97% pure determined by HPLC. The method developed demonstrates performing of reactive extraction on standard CCC as an option for separation of polar alkaloids from medicinal plants. [ABSTRACT FROM AUTHOR]

Shikimic acid (SA) is the drug lead of oseltamivir phosphate (Tamiflu®). The pharmaceutical industry has great demand for SA to match the production of the drug. This article describes the development of an integrated expanded-bed adsorption chromatography (EBAC) system and its application in SA extraction and separation. The hydrodynamic behavior of an expanded-bed ion exchange resin, D293, was investigated to show that D293 resin is able to act as an adsorbent for recovery of SA fromIllicium verum.SA was extracted from 8 g ofI. verumin 150 mL of deionized water at an expansion ratio of 1.4 via integrated EBAC at 40°C. The SA was then eluted in 200 mL of a 2% NaCl solution. The recovery rate of SA was 96.7% and its purity was 59.6%. Different methods were compared, and the results indicated that the method developed in this article is promising for the recovery of SA fromI. verum.The process efficiency of the integrated method was 2.6 times higher than that of the conventional method, while its energy efficiency was about 6 times of that of the conventional method. [ABSTRACT FROM AUTHOR]

• HS-SPME coupled with iBCF derivatization were used for determination SCFAs in fecal sample. • A method for determination of eleven SCFAs including formic acid in fecal sample was established. • The sensitivity of this method was much higher than other method. • The developed method showed a promising application in the analysis of SCFAs in biological sample. As metabolites of the gut microbiome, short-chain fatty acids (SCFAs) played an important role in the diagnosis of the metabolic diseases. Because of the high polarity, high volatility and complex matrix of biological samples, the highly sensitive, selective and accurate method to determine SCFAs remains a major challenge. Herein, a new method for simultaneous quantification of eleven SCFAs by derivatization combined with solid phase microextraction (SPME) and gas chromatography tandem mass spectrometry (GC–MS/MS) was developed. Isobutyl chloroformate coupled with isobutanol was used as the reaction reagent to derivatize SCFAs. The method validation data showed a satisfactory linearity with the linear regression coefficients (R) ranging from 0.9964 to 0.9996. The limit of detection (LOD) of all SCFAs ranges from 0.01 ng·mL−1 to 0.72 ng·mL−1 and the limit of quantification (LOQ) ranges from 0.04 ng·mL−1 to 2.41 ng·mL−1. The intra-day and inter-day precision (RSDs) ranged from 0.65% to 8.92% and 1.62% to 15.61%, respectively. The recovery ranged from 88.10% to 108.71%. Finally, the developed method was successfully used to determine SCFAs in mice fecal sample, and ten of the SCFAs were found in feces of mice, including formic acid. [ABSTRACT FROM AUTHOR]

A high-efficient and environmental-friendly method for the preparation of ginsenosides from Radix Ginseng using the method of coupling of ultrasound-assisted extraction with expanded bed adsorption is described. Based on the optimal extraction conditions screened by surface response methodology, ginsenosides were extracted and adsorbed, then eluted by the two-step elution protocol. The comparison results between the coupling of ultrasound-assisted extraction with expanded bed adsorption method and conventional method showed that the former was better than the latter in both process efficiency and greenness. The process efficiency and energy efficiency of the coupling of ultrasound-assisted extraction with expanded bed adsorption method rapidly increased by 1.4-fold and 18.5-fold of the conventional method, while the environmental cost and CO2 emission of the conventional method were 12.9-fold and 17.0-fold of the new method. Furthermore, the theoretical model for the extraction of targets was derived. The results revealed that the theoretical model suitably described the process of preparing ginsenosides by the coupling of ultrasound-assisted extraction with expanded bed adsorption system. [ABSTRACT FROM AUTHOR]

Abstract: This study developed a method for enriched separation of protopanaxatriol ginsenosides, malonyl ginsenosides and protopanaxadiol ginsenosides from Panax ginseng. The method began with targets extraction from herbal material, followed by HPD300 resins separation, then extracted by water-statured n-butanol. In the product achieved, protopanaxatriol ginsenosides were 24.4% pure with 70.9% recovery, malonyl ginsenosides were 33.4% pure with 23.3% recovery, and protopanaxadiol ginsenosides as well as Ro were 31.3% pure with 56.8% recovery. The adsorption test data on HPD300 resins fit the Langmuir model well. Moreover, the pseudo-first-order kinetic model showed the best correlation with the adsorption results. These findings indicate that the combination of HPD300 resin chromatography and water-statured n-butanol extraction effectively separates and enriches ginsenosides from P. ginseng. [Copyright &y& Elsevier]

Abstract: In this study, a method for the identification of flavonol and triterpene glycosides in Luo-Han-Guo extract using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) with personal database matching has been developed. Two flavonol glycosides and 20 triterpene glycosides were identified, and in addition the profiles of Luo-Han-Guo samples collected at different growing periods (15-, 40-, and 80-days) were compared. Principle component analysis (PCA) showed a clear separation among the various samples from different growing periods. The content of mogroside V significantly increased, while the level of mogroside IIE class dramatically decreased with an increase of growing time; however, the content of mogroside IV class was found to be high after a 40-day period of accumulation, but it subsequently decreased in the fully ripe period. Finally, 7 mogrosides could be screened as potential markers for discrimination of Luo-Han-Guo samples at different stages. The proposed analytical method combined with multivariate statistical analysis was shown to be a useful tool for investigating the chemical components of Luo-Han-Guo as well as for its quality evaluation. [Copyright &y& Elsevier]

Abstract: This article describes the development of an integrated expanded bed extraction and separation method for in-situ recovery of salvianolic acid B from Salvia miltiorrhiza Bunge. Twenty-five grams of the herb was extracted in a dynamic extraction column for 3h, while the target was simultaneously absorbed onto an expanded bed column without any further processing. Then, the expanded bed column was eluted with 1bed volume (BV) of water and 5BVs of 50% (v/v) ethanol aqueous solution with a flow rate of 2.4BV/h. From this, 1438.8mg of salvianolic acids, containing 55.7% of pure salvianolic acid B, was harvested with an 88.0% recovery. Six evaluation parameters – purity, recovery, process throughput, process efficiency, process environmental impact and general process evaluation – were used as indices for evaluation of different methods. The results indicate that the in-situ method we have developed is a promising process for the recovery of salvianolic acid B from the herb of S. miltiorrhiza Bunge. [Copyright &y& Elsevier]

• Polypyrrole-coated magnetic nanocomposites were creatively synthesized with the assistance of CTAB. • The kinetic and thermodynamic models were used to evaluate the adsorption performance of B-vitamins onto Fe 3 O 4 @PPy. • A method (MSPE/UPLC) for rapid extraction and detection of folic acid and riboflavin from human urine was developed. • The proposed method showed a promising application in the analysis of free folic acid and riboflavin in urine samples. Determination of folic acid and riboflavin in biological samples is difficult due to their high polarity, low concentration, chemical instability, and complex matrix. In this study, the polypyrrole-coated magnetic nanocomposite (Fe 3 O 4 @PPy) was synthesized innovatively with the assistance of hexadecyltrimethylammonium bromide. To evaluate the adsorption mechanism and the feasibility of synthesized Fe 3 O 4 @PPy as an adsorbent, the adsorption capacities, kinetics and thermodynamics of folic acid and riboflavin were investigated systemically. Furthermore, in light of the chemical instability of folic acid and riboflavin a method for rapid extraction and detection of them from human urine within 10 min was developed successfully by combining magnetic solid phase extraction with ultra-performance liquid chromatography (MSPE/UPLC). The adsorption parameters including sorbent amount, pH value, extraction time, desorption solvent and desorption time were studied. Under optimum conditions, the performance of the established determination method was validated with the linearly dependent coefficients (>0.9995), the limits of detection (0.02–0.05 µg/mL), the limits of quantification (0.07–0.18 µg/mL), and the recoveries (92.2–105.1%, with relative standard deviation < 3.3%). The rapid extraction and detection of folic acid and riboflavin from real urine samples were achieved subsequently. The present study suggests that the developed method exhibits a promising application in the analysis of free folic acid and riboflavin in human urine samples, which can provide a reference for the clinical drug monitoring and treatment. [ABSTRACT FROM AUTHOR]

• The chemical profile of ZSXBGZD as a whole was revealed for the first time. • Totally 148 compounds were identified in ZSXBGZD by the UPLC-Q-TOF-MS method. • An UPLC fingerprint with chemometrics was applied to ZSXBGZD from different origins. • 12 marker components of ZSXBGZD were simultaneously quantified by the UPLC method. Zhishi-Xiebai-Guizhi Decoction (ZSXBGZD), a traditional Chinese medicine (TCM) formula, has been used for treatment of coronary heart disease and myocardial infarction for nearly two thousand years. However, the chemical composition of ZSXBGZD is still unclear. In order to obtain the chemical profile of ZSXBGZD, an ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method was utilized for the identification of its multi-constituents. As a result, a total of 148 compounds were identified based on their retention times, accurate masses and MS/MS data. In addition, an optimized UPLC fingerprint analysis, combined with chemometrics such as similarity analysis (SA), hierarchical cluster analysis (HCA), principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) was developed for quality assessment of ZSXBGZD. Multivariate data analysis revealed that samples could be classified correctly according to their geographic origins, and four compounds neohesperidin, naringin, guanosine and adenosine contributed the most to classification. The established UPLC method with multi-wavelength detection was further validated and implemented for simultaneous quantification of 12 representative ingredients in the prescription, including guanosine, adenosine, 2′-deoxyadenoside, syringin, magnoloside A, forsythoside A, naringin, hesperidin, cinnamaldehyde, neohesperidin, honokiol and magnolol. This is the first report on the comprehensive profiling of major chemical components in ZSXBGZD. The results of the study could help to uncover the chemical basis of ZSXBGZD and possess potential value for quality evaluation purpose. [ABSTRACT FROM AUTHOR]

A new reaction based fluorescence turn-off strategy for detection of secondary amines was developed. The probe shows fast response and high selectivity to secondary amines in solution/film at sub-ppm levels through chromogenic and fluorescent dual-mode signal changes. [ABSTRACT FROM AUTHOR]

Arabidopsis thaliana natural resistance-associated macrophage protein 3 (AtNRAMP3) is involved in the transport of cadmium (Cd), iron (Fe), and manganese (Mn). Here, we present a structure-function analysis of AtNRAMP3 based on site-directed mutagenesis and metal toxicity growth assays involving yeast mutants, combined with three-dimensional (3D) structure modeling based on the crystal structure of the Eremococcus coleocola NRAMP family transporter, EcoDMT. We demonstrated that two conservative sites, D72 and N75, are essential for the transport activity. The M248A mutation resulted in a decrease in Cd sensitivity, while maintaining Mn transport. The mutation involving G61 caused a significant impairment of Fe and Mn transport, thereby indicating the importance of the conserved residue for proper protein function. The mutation involving G171 disrupted Fe transport activity but not that of Mn and Cd, suggesting that G171 is essential to metal binding and selectivity. Two residues, E194 and R262, may play an important role in stabilizing outward-facing conformation, which is essential for transport activity. Deletion assays indicated that the N-terminus is necessary for the function of AtNRAMP3. The findings of the present study revealed the structure-function relationship of AtNRAMP3 and metal transport activity and selectivity, which may possibly be applied to other plant NRAMP proteins. [ABSTRACT FROM AUTHOR]