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Ethnopharmacological Relevance: Radix Bupleuri (Bupleurum chinense DC.) is the most commonly used traditional Chinese medicine (TCM) for the treatment of liver diseases. While the effects of Radix Bupleuri (BR) on lipid-lowering and liver protection have been established, its role in the development of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet remains unclear., Aim of the Study: The objective of this study was to evaluate the alleviation effects of the active fraction of BR on NAFLD in vivo and to explore the underlying mechanisms through an analysis of liver transcriptome and lipidomics., Materials and Methods: The NAFLD model was established in SD rats by administering a high-fat diet (HFD) for 8 weeks. Subsequently, the NAFLD model rats were continuously gavaged with different polarity fractions of BR (25 g/kg/d) and melatonin (MT) (30 mg/kg/d) for an additional 6 weeks to assess therapeutic effects. The potential mechanism of the low polarity fraction of BR (LBR) in treating NAFLD was investigated through hepatic transcriptome analysis, non-targeted lipidomics, RT-qPCR, protein-protein interaction (PPI) network construction, molecular docking, and Western blotting, aiming to elucidate the underlying mechanisms by which LBR may ameliorate NAFLD., Results: These results demonstrated that LBR significantly alleviated the effects of HFD-induced NAFLD, as evidenced by reductions in body weight (BW), liver weight (LW), and epididymal fat weight (EFW) compared to model rats and other polarity fractions of BR. Furthermore, LBR notably down-regulated serum and liver levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while up-regulating high-density lipoprotein cholesterol (HDL-C) in serum. Mechanistically, liver transcriptome analysis indicated that fatty acid metabolism may be a crucial pathway for the improvement of NAFLD following LBR treatment. Lipidomics data suggested that LBR can modulate the metabolic profile in NAFLD rats. Enrichment analysis revealed that glycerophospholipid and glycerolipid metabolism might be key pathways involved in the development of NAFLD. RT-qPCR analysis demonstrated that LBR could regulate the expression of lipid-related genes in these critical pathways. Additionally, Spearman correlation analysis showed a strong relationship between lipid metabolic biomarkers, pathological indices, and lipid-related genes. Moreover, protein-protein interaction (PPI) network and molecular docking analyses identified seven key targets with six ingredients of LBR exhibiting good binding capacity (<-5.0 kcal/mol). Finally, Western blotting analysis indicated that LBR up-regulates the expression levels of PPARα, CPT1, and FABP1 while down-regulating the expression levels of SREBF1 and SCD1, thereby improving metabolism and exerting a lipid-lowering effect., Conclusion: In conclusion, the present research elucidated the lipid-lowering mechanisms of the active fractions of BR. Both BR and LBR presented themselves as promising candidates for the development of novel pharmacological agents targeting NAFLD. LBR effectively ameliorated lipid disturbances associated with HFD-induced NAFLD by modulating the metabolism of fatty acids, cholesterol, glycerolipid, and glycerophospholipids. Consequently, LBR held significant potential for development as an effective lipid-lowering therapeutic., 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.)

A strategically designed ternary nanohybrid (TNS-PDA/CNT), consisting of titanate nanosheet (TNS) and polydopamine-modified multiwalled carbon nanotube (PDA/CNT composite), was synthesized by the facile hydrothermal method and wet impregnation method for removal of U(VI) from aqueous solution and were characterized by transmission electron microscopy (TEM), scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDS), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), Raman spectroscopy, Brunauer-Emmett-Teller (BET), and X-ray photoelectron spectroscopy (XPS). TNSs were introduced into the PDA/CNT composite, which effectively averted the agglomeration of the CNT and further exposed more adsorption sites. PDA thin layer exposing more active sites was conducive to enhance adsorption capacity and kinetic. The adsorption process was largely influenced by pH values and weakly affected by ionic strength, indicating that the adsorption process was controlled by inner-sphere surface complexes because of TNS-PDA/CNT with multiple functional groups, including imine, catechol, amine, and hydroxyl groups. The isotherm data could be well described by the Langmuir model, and the monolayer maximum adsorption was determined to be 309.60 mg/g at pH = 5.0 and temperature = 45 °C. Thermodynamic parameters (Δ G ° < 0, Δ S ° > 0, and Δ H ° < 0) showed that the nature of adsorption was endothermic and spontaneous. By XRD, FT-IR, and XPS analyses, the adsorption mechanism mainly involved surface complexation and ion exchange. In summary, the TNS-PDA/CNT materials are fully qualified as a satisfactory adsorbent for the purification and recovery of U(VI) from wastewater., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Arsenic (As) pollution in water poses a significant threat to the ecological environment and human health. Meanwhile, the resource utilisation of coal gangue is of utmost importance in ecologically sustainable development. Thus, the FeOOH@coal gangue composite (FeOOH@CG) was synthesised for As(V) adsorption in this study. The results showed that α-FeOOH, β-FeOOH and Schwertmannite loaded on the surface of FeOOH@CG. Moreover, the adsorption behaviour of As(V) by FeOOH@CG was investigated under different reaction conditions, such as pH, contact time, initial concentration and co-existing anions. The optimum adsorption conditions were as follows: initial As(V) concentration of 60 mg/L, pH of 3.0 and adsorption time of 180-240 h. The adsorption capacity of FeOOH@CG for As(V) was pH-dependent and the maximum adsorption capacity was 185.94 mg/g. The presence of anions ( H 2 PO 4 - , HCO 3 - and C l - ) decreased the adsorption efficiency of FeOOH@CG for As(V). The adsorption process of FeOOH@CG for As(V) could be well-described by the pseudo-second-order model and Langmuir model, indicating that the adsorption process mainly depended on chemical adsorption. The thermodynamic analysis suggested that the adsorption was a spontaneous and endothermic process. In addition, according to the analyses of XRD, FTIR and XPS, the dominant mechanisms of As(V) adsorption by FeOOH@CG were electrostatic attraction, complexation and precipitation. In conclusion, FeOOH@CG has great potential as an efficient and environmentally friendly adsorbent for As(V) adsorption from aqueous solution.

Evaluating the impact of large-scale human activities on carbon storage through land use changes is of growing interest in terrestrial ecosystem assessments. The Huaihe River Basin, a vital Chinese grain production area, has undergone marked land use changes amid socio-economic acceleration. Evaluating the impacts of land use change on carbon storage and future carbon sequestration is imperative for regional ecosystem sustainability and Chinese food security, simultaneously, furnishing data support to regional land use planning and decision-making processes. Nonetheless, the mechanisms linking land use changes to carbon storage and the future carbon reservoir responses remain unclear. We utilized a multi-source dataset and representative scenarios, integrating PLUS, InVEST models, and Geodetector to assess land use change impacts on carbon storage in the Huaihe River Basin (2000-2030). The data indicates the following: (1) from 2000 to 2020, cultivated land decreased by 28,344.69 km 2 , construction land increased by 26,914.56 km 2 , and other land types changed little. (2) Land use change resulted a carbon loss of 1.17 × 10 8 t, primarily due to the expansion of construction land. (3) All four simulation scenarios exhibited diminished carbon storage relative to 2020, with the economic development scenario recording the lowest at 4.98 × 10 9 t and the ecological protection scenario the highest at 5.06 × 10 9 t. (4) Elevation predominantly drives carbon storage changes, with its interaction with NPP having the greatest impact. The factors synergistically enhance their explanatory power. The research provides a scientific basis for strategies aimed at augmenting regional carbon sequestration and refining low-carbon land management, safeguarding ecosystem stability., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The rapid development of deep learning techniques has driven the emergence of a neural network-based variational Monte Carlo (VMC) method (referred to as FermiNet), which has manifested high accuracy and strong predictive power in the electronic structure calculations of atoms, molecules, and some periodic systems. Recently, the implementation of the effective core potential (ECP) scheme has further facilitated more efficient calculations in practice. However, there is still a lack of comprehensive assessments of the ECP's performance under the FermiNet. In this work, we set sail to fill this gap by conducting extensive tests on the first two row elements regarding their atomic, spectral, and molecular properties. Our major finding is that, in general, the qualities of ECPs have been correctly reflected under FermiNet. Two recently built ECP tables, namely, correlation consistent ECP (ccECP) and energy consistent correlated electron pseudopotential (eCEPP), seem to prevail in terms of overall performance. In particular, ccECP performs slightly better on spectral precision and covers more elements, while eCEPP is more systematically built from both shape and energy consistency and better treats the core polarization. On the other hand, the high accuracy of the all-electron calculations is hindered by the absence of relativistic effects as well as the numerical instabilities in some heavier elements. Finally, with further in-depth discussions, we generate possible directions for developing and improving FermiNet in the near future., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Ethnopharmacological Relevance: Conventional antidepressants therapy remains unsatisfactory due to the disadvantages of delayed clinical onset of action and side effects. Traditional Chinese Medicine (TCM) with good efficacy and higher safety have received much attention. Angelicae Sinensis Radix (AS), a well-known TCM, has been proved to exhibit the efficacy of antidepression recently., Aim of the Study: The purpose of this study was to investigate the potential anti-depressant mechanisms of AS based on chronic unpredictable mild stress (CUMS) rat model., Materials and Methods: In this study, behavioral experiments, molecular biology techniques, and ultra performance liquid chromatography-triple-time of flight mass spectrometer (UPLC-Triple-TOF/MS) were combined to explore the potential antidepressant mechanisms of AS based on CUMS rat model., Results: The results demonstrated that AS could reduce the contents of serum hypothalamic-pituitary-adrenal (HPA) axis hormones in CUMS rats, including corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol (CORT). In addition, AS regulated the percentage of CD4 + T lymphocytes, the ratio of CD4 + /CD8 + , and the levels of serum cytokines such as IL-1β, IL-4, IL-6, and TNF-α in CUMS rats. Lipidomics showed that 31 lipids were related to depression and AS could regulate the lipid metabolism alteration induced by CUMS, particularly sphingolipid metabolism. Finally, the key proteins in sphingolipid metabolic pathways in hippocampus of CUMS rats could be back-regulated by AS, including serine palmitoyl transferase (SPTLC2), ceramide synthase (CerS2), sphingomyelinase (SPHK1), and neutral sphingomyelinase (nSMase)., Conclusion: AS could alleviate NEI network disorder and restore the levels of sphingolipid metabolites and key proteins in CUMS rats. The underlying mechanism by which AS relieved depression-like behavior in CUMS rats may be through modulation of NEI and disturbances in sphingolipid metabolism., 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 © 2023 Elsevier B.V. All rights reserved.)

Chaigui granules (CG) are a compound composed of six herbal medicines with significant antidepressant effects. However, the antidepressant mechanism of CG remains unclear. In the present study, we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling. First, the regulatory effect of CG on purine metabolites in the prefrontal cortex (PFC) of chronic unpredictable mild stress (CUMS) rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) targeted quantitative analysis. Meanwhile, purinergic receptors (P2X7 receptor (P2X7R), A 1 receptor (A 1 R) and A 2A receptor (A 2A R)) and signaling pathways (nod-like receptor protein 3 (NLRP3) inflammasome pathway and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway) associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay (ELISA). Besides, antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro. An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG. Additionally, purinergic receptors (P2X7R, A 1 R and A 2A R) and related signaling pathways (NLRP3 inflammasome pathway and cAMP-PKA pathway) were also significantly regulated by CG. The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway, and the reduction of adenosine and inosine inhibited the A 1 R-cAMP-PKA pathway, which was significantly ameliorated by CG. Overall, CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A 1 R-cAMP-PKA pathway., (© 2023 The Authors.)

Remediation of arsenic (As) and cadmium (Cd) co-contaminated soil is a challenge in environmental remediation. In this study, coal gangue-based magnetic porous material (MPCG) was designed for simultaneous immobilization of As and Cd in contaminated soil. After the incubation experiment, the effects of CG and MPCG on the availability and fractions of As and Cd and the related microbial functional genes were analyzed to explore the potential remediation mechanisms of MPCG for As and Cd in contaminated soil. The results showed that the stabilization effect of MPCG on As and Cd was significantly higher than that of coal gangue. It reduced the available As and Cd by 17.94-29.81% and 14.22-30.41%, respectively, and transformed unstable As/Cd to stable. The remediation mechanisms of MPCG on As included adsorption, oxidation, complexation and precipitation/co-precipitation. Meanwhile, the remediation mechanisms of MPCG for Cd included adsorption, ion exchange, complexation and precipitation. In addition, MPCG increases the abundance of sulfate-reducing bacteria (dsrA) by 43.39-381.28%, which can promote sulfate reduction. The sulfide can precipitate with As and Cd to reduce the availability of As and Cd in soil. Thus, MPCG is a promising amendment for achieving the remediation of As and Cd co-contaminated soil., 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 © 2023. Published by Elsevier Ltd.)

Objectives: Scutellaria baicalensis leaf (SLE), the above-ground part of the traditional Chinese medicine Scutellaria baicalensis Georgi, is rich in resources and contains a large number of flavonoids with anti-inflammatory, antioxidant and neuroprotective functions. The present study evaluated the ameliorative effects and related mechanisms of SLE on d-gal-induced ageing rats, providing a theoretical basis for the exploitation of SLE., Methods: This experiment investigated the mechanism of SLE for anti-ageing by non-targeted metabonomics technology combined with targeted quantitative analysis and molecular biology technology., Key Findings: Non-targeted metabonomics analysis showed that 39 different metabolites were screened out. Among them, 38 metabolites were regulated by SLE (0.4 g/kg), and 33 metabolites were regulated by SLE (0.8 g/kg). Through enrichment analysis, glutamine-glutamate metabolic pathway was identified as the key metabolic pathway. Subsequently, the results of targeted quantitative and biochemical analysis displayed that the contents of key metabolites and the activities of enzymes in glutamine-glutamate metabolic pathway and glutathione synthesis could be regulated by SLE. Furthermore, the results of Western blotting indicated that SLE significantly modulated the expression of Nrf2, GCLC, GCLM, HO-1, and NQO1 proteins., Conclusion: To sum up, the anti-ageing mechanism of SLE was related to glutamine-glutamate metabolism pathway and Nrf2 signalling pathway., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Leucine is a common nutritional supplement, and recently, research concerned with the improvement role of leucine in neuropsychiatric disorders has been increasingly emphasized. However, it is unclear what role leucine plays in depression. In this study, the chronic social defeat stress (CSDS) model was used to simulate depression associated with social avoidance in humans. CSDS mice display a depressive state and social avoidance behavior. Untargeted serum metabolomics and pathway analysis indicated that abnormal amino acid metabolism may be the key to abnormal behavior in CSDS mice. Among these metabolites, leucine shows a specific and significant positive correlation with social interaction rate. Targeted metabolomics determine the decreased level of leucine and related metabolites in the serum and hippocampus of CSDS mice. Moreover, immunohistochemical results also indicate an increasing expression of IDO1 in hippocampal tissues in CSDS mice, and neurons may be damaged. Subsequently, leucine was administered to investigate its influence on CSDS mice, and the results revealed that leucine had a good effect on depressive states and social avoidance behaviors. Taken together, we aim to identify the important role of leucine as a functional food supplement to improve depression and social avoidance behavior through the above findings.

Radix Bupleuri (RB) is commonly used to treat depression, but it can also lead to hepatotoxicity after long-term use. In many anti-depression prescriptions, RB is often used in combination with Radix Paeoniae Alba (RPA) as an herb pair. However, whether RPA can alleviate RB-induced hepatotoxicity remain unclear. In this work, the results confirmed that RB had a dose-dependent antidepressant effect, but the optimal antidepressant dose caused hepatotoxicity. Notably, RPA effectively reversed RB-induced hepatotoxicity. Afterward, the mechanism of RB-induced hepatotoxicity was confirmed. The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase (GSS) activity in the liver, and further cause liver injury through oxidative stress and nuclear factor kappa B (NF-κB)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. Furthermore, the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated. The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity, thereby promoting the conversion of saikosaponins to saikogenins in vivo. Different from saikosaponin A and saikosaponin D, which are directly combined with GSS as an inhibitor, their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity. Based on this, RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NF-κB/NLRP3 pathway. In conclusion, the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Author(s).)

The prediction of the spatiotemporal dynamic evolution of vegetation cover in the Huainan mining area and the quantitative evaluation of its driving factors are of great significance for protecting and restoring the environment in this area. This study uses the Landsat 5 TM and Landsat 8 OLI time-series data to estimate the vegetation cover and uses the transition matrix to analyze the spatiotemporal transfer of vegetation cover from 1989 to 2004, 2004 to 2021, and 2021 to 2030. In addition, a structural equation model (SEM) was established in this study to assess the driving factors of vegetation cover. The quantitative analysis and the cellular automata (CA)-Markov model were performed to predict the future vegetation cover in the Huainan mining area. The results are as follows: (1) In different periods, the vegetation cover types were mainly high cover types transferred to other vegetation cover types; (2) human activities are the key factors affecting the vegetation growth, while topographical factor is the most influential factor promoting the vegetation growth; (3) highly consistent CA-Markov and multi-criteria evaluation (MCE) predicted results of vegetation cover in 2030 compared to that in 2021. The proportion of bare soil and low cover types had increased significantly, mainly concentrated in the internal area of the mines. The prediction of the spatiotemporal evolution of vegetation cover in the Huainan mining area and the quantitative change in driving factors are of significant importance for the restoration of the environment in mining areas., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Ethnopharmacological Relevance: Bupleurum chinense DC-Paeonia lactiflora Pall (BCD-PLP) is a common clinical herb pair in traditional Chinese medicine (TCM) prescriptions commonly used to treat depression. However, its combination mechanisms with its anti-depressive effects remain highly unclear., Aim of the Study: Here, an effective strategy has been developed to study the combination mechanisms of Bupleurum chinense DC (BCD) and Paeonia lactiflora Pall (PLP) by integrating serum pharmacochemistry analysis, metabolomics technology, and molecular docking technology., Materials and Methods: First, the depression model rats were replicated by the chronic unpredictable mild stress (CUMS) procedure, and the difference in the chemical composition in vivo before and after the combination of BCD and PLP was analyzed by integrating background subtraction and multivariate statistical analysis techniques. Then, UPLC/HRMS-based serum metabolomics was performed to analyze the synergistic effect on metabolite regulation before and after the combination of BCD and PLP. Further, the correlation analysis between the differential exogenous chemical components and the differential endogenous metabolites before and after the combination was employed to dissect the combination mechanisms from a global perspective of combining metabolomics and serum pharmacochemistry. Finally, the molecular docking between the differential chemical components and the key metabolic enzymes was applied to verify the regulatory effect of the differential exogenous chemical components on the differential endogenous metabolites., Results: The serum pharmacochemistry analysis results demonstrated that the combination of BCD and PLP could significantly affect the content of 10 components in BCD (including 5 prototype components were significantly decreased and 5 metabolites were significantly increased) and 8 components in PLP (including 4 prototype components and 3 metabolites were significantly increased, 1 metabolite was significantly decreased), which indicated that the combination could enhance BCD prototype components' metabolism and the absorption of the PLP prototype components. Besides, metabolomics results indicated that the BCD-PLP herb pair group significantly reversed more metabolites (8) than BCD and PLP single herb group (5 & 4) and has a stronger regulatory effect on metabolite disorders caused by CUMS. Furthermore, the correlation analysis results suggested that saikogenin F and saikogenin G were significantly positively correlated with the endogenous metabolite itaconate, an endogenous anti-inflammatory metabolite; and benzoic acid was significantly positively correlated with D-serine, an endogenous metabolite with an antidepressant effect. Finally, the molecular docking results further confirmed that the combination of BCD and PLP could affect the activities of cis-aconitic acid decarboxylase and D-amino acid oxidase by increasing the in vivo concentration of saikogenin F and benzoic acid, which further enhances its anti-inflammatory activity and anti-depressive effect., Conclusions: In this study, an effective strategy has been developed to study the combination mechanisms of BCD and PLP by integrating serum pharmacochemistry analysis, multivariate statistical analysis, metabolomics technology, and molecular docking technology. Based on this strategy, the present study indicated that the combination of BCD and PLP could affect the activities of cis-aconitic acid decarboxylase and D-amino acid oxidase by increasing the concentration of saikogenin F and benzoic acid in vivo, which further enhances its anti-depressive effect. In short, this strategy will provide a reliable method for elucidating the herb-herb compatibility mechanism of TCM., 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 © 2022 Elsevier B.V. All rights reserved.)

Land use demand change in the Huaihe River basin (HRB) and ecosystem service values (ESVs) in watersheds are important for the sustainable development and use of land resources. This paper takes the HRB as the research object, and using remote sensing images of land use as the data source adopts the comprehensive evaluation analysis method of ESVs based on equivalent factors and sensitivity analysis of the performance characteristics of ESV changes of different land use types. The PLUS model is used to predict spatiotemporal land use change characteristics to 2030 combining inertial development, ecological development, and cultivated land development. The spatial distribution and aggregation of ESVs at each scale were also explored by analyzing ESVs at municipal, county, and grid scales. Considering also hotspots, the contribution of land use conversion to ESVs was quantified. The results showed that (1) from 2000 to 2020, cultivated land decreased sharply to 28,344.6875 km 2 , while construction land increased sharply to 26,914.563 km 2 , and the change of other land types was small. (2) The ESVs in the HRB were 222,019 × 10 12 CNY in 2000, 235,015 × 10 12 CNY in 2005, 234,419 × 10 12 CNY in 2010, 229,885 × 10 12 CNY in 2015, and 224,759 × 10 12 CNY in 2020, with an overall fluctuation, first increasing and then decreasing. (3) The ESVs were 219,977 × 10 12 CNY, 218,098 × 10 12 CNY, 219,757 × 10 12 CNY, and 213,985 × 10 12 CNY under the four simulation scenarios of inertial development, ecological development, cultivated land development, and urban development, respectively. At different scales, the high-value areas decreased, and the low-value areas increased. (4) The hot and cold spots of ESV values were relatively clustered, with the former mainly clustered in the southeast region and the latter mainly clustered in the northwest region. The sensitivity of ecological value was lower than 1, while the ESV was inelastic to the ecological coefficient, and the results were plausible. The mutual conversion of cultivated land to water contributed the most to ESVs. Based on the multi-scenario simulation of land use in the HRB by the PLUS model, we identified the spatial distribution characteristics of ESVs at different scales, which can provide a scientific basis and multiple perspectives for the optimization of land use structure and socio-economic development decisions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Angelicae Sinensis Radix (AS) is reproted to exert anti-depression effect (ADE) and nourishing blood effect (NBE) in a rat model of depression. The correlation between the two therapeutic effects and its underlying mechanisms deserves further study. The current study is designed to explore the underlying mechanisms of correlation between the ADE and NBE of AS based on hepatic metabonomics, network pharmacology and molecular docking. According to metabolomics analysis, 30 metabolites involved in 11 metabolic pathways were identified as the potential metabolites for depression. Furthermore, principal component analysis and correlation analysis showed that glutathione, sphinganine, and ornithine were related to pharmacodynamics indicators including behavioral indicators and hematological indicators, indicating that metabolic pathways such as sphingolipid metabolism were involved in the ADE and NBE of AS. Then, a target-pathway network of depression and blood deficiency syndrome was constructed by network pharmacology analysis, where a total of 107 pathways were collected. Moreover, 37 active components obtained from Ultra Performance Liquid Chromatography-Triple-Time of Flight Mass Spectrometer (UPLC-Triple-TOF/MS) in AS extract that passed the filtering criteria were used for network pharmacology, where 46 targets were associated with the ADE and NBE of AS. Pathway enrichment analysis further indicated the involvement of sphingolipid metabolism in the ADE and NBE of AS. Molecular docking analysis indciated that E-ligustilide in AS extract exhibited strong binding activity with target proteins (PIK3CA and PIK3CD) in sphingolipid metabolism. Further analysis by Western blot verified that AS regulated the expression of PIK3CA and PIK3CD on sphingolipid metabolism. Our results demonstrated that sphingolipid metabolic pathway was the core mechanism of the correlation between the ADE and NBE of AS., (Copyright © 2023 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

The present study aimed to evaluate the anti-aging effect of the leaves of Scutellaria baicalensis Georgi (LSBG) and investigate its mechanisms. For this purpose, SD rats were received D-galactose (D-gal) subcutaneously (0.3 g/kg) and LSBG intragastrically (0.4 g/kg or 0.8 g/kg) for 7 weeks. Behavior tests were conducted to evaluate the cognitive function of all rats. Results showed that memory impairment was reversed by LSBG. Then, metabolomics of the cortex and hippocampus were used to investigate the potential mechanisms. 21 metabolites in the cortex and 22 metabolites in the hippocampus of aging rats were altered, respectively. Additionally, results showed that the content of key metabolites and activities of enzymes in glutamate metabolism and its downstream metabolism (glutathione metabolism) could be regulated by the LSBG. Additionally, proteins in the Nrf2 signaling pathway were analyzed by western blot. And the protein expression levels of Nrf2, GCLC, HO-1, NQO-1 were significantly regulated by the LSBG in the cortex and hippocampus. Above all, the anti-aging effects of the LSBG were involved in regulating the glutamate metabolism and Nrf2 signaling pathway., 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 © 2022 Elsevier Inc. All rights reserved.)

Background: Saikosaponin A (SSA) and albiflorin (AF) are major bioactive compounds of Radix Bupleuri and Radix Paeoniae alba respectively, which possess antidepressant effects in pharmacological experiments. However, whether SSA and AF have synergistic neuroprotective effects and the synergistic mechanisms are still unknown., Methods and Results: The corticosterone-induced PC12 cells apoptosis model was employed to assess the neuroprotective effects of SSA and AF, and the synergistic effect was analyzed using three mathematical models. Meanwhile, cell metabolomics was used to detect the effects on metabolite regulation of SSA and AF. Furthermore, the key metabolites, metabolic enzymes, and cellular markers were verified by ELISA and Western blotting. The results showed that the combination of SSA and AF has a synergistic neuroprotective effect. Besides, the combination could regulate more metabolites than a single agent and possessed a stronger adjustment effect on metabolites. The TCA cycle was regulated by SSA and AF via improving mitochondrial function. The purine metabolism was regulated by SSA via inhibition xanthine oxidase activity and the glutamate metabolism was regulated by AF via inhibition glutaminase activity. Moreover, the oxidative stress induced by the purine metabolism was attenuated by SSA via a reduction in the ROS level. Additionally, the inflammation induced by the oxidative stress was attenuated by the SSA and AF via inhibition of the NLRP3 protein expression., Conclusions: This study for the first time demonstrated the synergistic neuroprotective effects of SSA and AF, and the synergistic mechanisms were involved in metabolic disorders regulation and neuroinflammation inhibition., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Bupleurum chinense DC (Chaihu) -Paeonia lactiflora Pall (Baishao) is among the most accepted herb pairs in many classic antidepressant prescriptions. Our previous study has shown that the Chaihu-Baishao herb pair (CBHP) had a better antidepressant effect than Chaihu or Baishao. Nevertheless, the synergistic antidepressant mechanism of this herb pair was not clearly understood. This study aimed to investigate the compatibility mechanism of Chaihu and Baishao for treating depression through a strategy of non-targeted metabolomics combined with targeted quantitative analysis and molecular biology techniques. First, the compatibility effects of CBHP were assessed by the chronic unpredictable mild stress (CUMS) rat model. Next, cortex metabolomics based on ultra-high-performance liquid chromatography combined with quadrupole orbitrap mass spectrometry (UPLC-Q-Orbitrap/MS) was used to discover the metabolic pathway that was synergistically regulated by CBHP. Based on the results of metabolomics analysis, metabolites were quantitatively validated by UPLC-MS/MS combined with the MRM mode in the crucial metabolic pathway. In addition, the signaling pathway associated with this metabolic pathway was detected by molecular biology techniques to further identify the biological meaning of the crucial metabolite on the synergistic antidepressant effect of CBHP. The antidepressant effect of CBHP was significantly better than that of Chaihu or Baishao single administrated in the behavioral test. According to cortex metabolomics, a total of 21 differential metabolites were screened out, and purine metabolism was selected as the crucial metabolic pathway by the enrichment analysis of differential metabolites. Subsequently, purine metabolism was confirmed as disorder in the CUMS group by targeted quantitative analysis, CBHP regulated more purine metabolites (six) than individual administration (two and two). The results showed that purine metabolism was modulated by CBHP through synergistically decreasing xanthine levels and inhibiting the conversion of xanthine dehydrogenase (XDH) to xanthine oxidase (XOD). Finally, the synergistic regulation effect of CBHP on xanthine synthesis was found to be related to inhibition of malondialdehyde (MDA) production, Nod-like receptor protein 3 (NLRP3) inflammasome expression, and interleukin (IL)-1 β , IL-6, and tumor necrosis factor (TNF)- α secretion. The present study demonstrated that the regulation of purine metabolism, the suppression of oxidative stress, and inflammatory responses in the cortex were involved in the synergistic antidepressant effect of CBHP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Li, Qin, Du and Zhou.)

Reproductive-stage heat stress (RSHS) poses a major constraint to cereal crop production by damaging main plant reproductive structures and hampering reproductive processes, including pollen and stigma viability, pollination, fertilization, grain setting and grain filling. Despite this well-recognized fact, research on crop heat stress (HS) is relatively recent compared to other abiotic stresses, such as drought and salinity, and in particular, RSHS studies in cereals are considerably few in comparison with seedling-stage and vegetative-stage-centered studies. Meanwhile, climate change-exacerbated HS, independently or synergistically with drought, will have huge implications on crop performance and future global food security. Fortunately, due to their sedentary nature, crop plants have evolved complex and diverse transient and long-term mechanisms to perceive, transduce, respond and adapt to HS at the molecular, cell, physiological and whole plant levels. Therefore, uncovering the molecular and physiological mechanisms governing plant response and tolerance to RSHS facilitates the designing of effective strategies to improve HS tolerance in cereal crops. In this review, we update our understanding of several aspects of RSHS in cereals, particularly impacts on physiological processes and yield; HS signal perception and transduction; and transcriptional regulation by heat shock factors and heat stress-responsive genes. We also discuss the epigenetic, post-translational modification and HS memory mechanisms modulating plant HS tolerance. Moreover, we offer a critical set of strategies (encompassing genomics and plant breeding, transgenesis, omics and agronomy) that could accelerate the development of RSHS-resilient cereal crop cultivars. We underline that a judicious combination of all of these strategies offers the best foot forward in RSHS tolerance improvement in cereals. Further, we highlight critical shortcomings to RSHS tolerance investigations in cereals and propositions for their circumvention, as well as some knowledge gaps, which should guide future research priorities. Overall, our review furthers our understanding of HS tolerance in plants and supports the rational designing of RSHS-tolerant cereal crop cultivars for the warming climate.

Colorimetric sensing is a low-cost, intuitive method for monitoring the freshness of food. We prepared a colorimetric strip sensor array by mixing different amounts of bromophenol blue (BPB) and bromocresol green (BCG). As results of NH 3 simulation, the array strip turned from yellow to blue, and the number of blue spots increased with the increasing NH 3 , like a progress bar. Although the actual color is quite different, the color-changing trend was consistent with the simulated model calculated by a computer. The progress bar results remained stable under three lighting conditions. Furthermore, in the Cod preservation experiment, the color-changing progress of the strip sensor array is consistent with the simulation and can indicate Cod freshness while providing more distinguish levels. Therefore, a "progress bar" indicator built by this strategy possess the potential of realizing nondestructive, more accurate, and commercially available food quality monitoring through the naked eye and smart equipment recognition., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chaigui granules were a traditional Chinese medicine (TCM) preparation with antidepressant effects derived from a famous antidepressant prescription. It was of great significance to clarify the antidepressant mechanism of Chaigui granules for the clinical application of this drug. In this study, a chronic unpredictable mild stress (CUMS) depression model was successfully established, and behavioral indicators were used to evaluate the antidepressant effect. Second, the CD4+, CD8+, and CD4+/CD8+ levels were detected in peripheral blood. Meanwhile, the amount of inflammatory cytokines was determined in serum. Correspondingly, LC/MS-based peripheral blood mononuclear cell (PBMC) metabolomics was used to investigate vital metabolic pathways participating in the antidepressive effects of Chaigui granules. Finally, bioinformatics technology was further employed to discover the potential antidepressant mechanism of Chaigui granules regulating the immune system. The results suggested that the administration of Chaigui granules significantly improved CUMS-induced depressive symptoms. Chaigui granules could improve immune function by regulating T lymphocyte subsets, increasing anti-inflammatory cytokine levels of IL-2 and IL-10, and reducing pro-inflammatory cytokine levels of TNF-α, IL-1β, and IL-6. In addition, metabolomics results of PBMCs showed that Chaigui granules improved 14 of the 25 potential biomarkers induced by CUMS. Metabolic pathway analyses indicated that purine metabolism was the critical metabolic pathway regulated by Chaigui granules. Furthermore, correlation analysis indicated that 13 key biomarkers were related to immune-related indicators. The metabolite-gene network of 13 key biomarkers was investigated by using bioinformatics. The investigation showed that 10 targets (5'-nucleotidase ecto; 5'-nucleotidase, cytosolic IB; 5'-nucleotidase, cytosolic II; etc.), mainly belong to the purine metabolism, might be potential targets for Chaigui granules to exert their antidepressant effects by improving immune function impairment. Together, our results suggested that Chaigui granules might exert antidepressant effects by improving immune function and regulating the purine metabolic pathway in PBMCs. This work used PBMCs metabolomics as an entry point to study the antidepressant mechanism of Chaigui granules, which provided a new way to elucidate the mechanism of a traditional Chinese medicine prescription., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A nanocomposite of a zirconium-based metal-organic framework (UiO-66) @ polypyrrole (PPy) (UiO-66@PPy) was successfully synthesized to eliminate F - from groundwater. The optimum initial pH and adsorbent dose for maximum uptake of F - from aqueous solution were found to be 3.0 and 0.1 g/L, respectively. The fluoride removal performance of UiO-66 was greatly enhanced through the introduction of polypyrrole guests, and the maximum adsorption capacity of UiO-66@PPy, namely, 290.7 mg/g, was reached, which is far superior to those of other previously reported adsorbents. The fluoride adsorption by UiO-66@PPy agreed well with the pseudo-second-order equation model and Langmuir isotherm model. The coexisting PO 4 3- and CO 3 2- substantially influence fluoride removal. The synthesized UiO-66@PPy could be reused five times in adsorption-desorption cycles. The incorporation of conducting polymers opened additional paths for the development of adsorbent materials; thus, UiO-66@PPy could be a viable adsorbent material and contribute to fluoride removal from groundwater., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: Radix Bupleuri-Radix Paeoniae Alba (BP), a traditional Chinese medicine herb pair, has treated depression by coordinating the liver in Chinese classical medicine books and modern research. This study aims to verify the antidepressant effect of BP by behavioural examination, and reveal the underlying antidepressant mechanisms of BP., Methods: The antidepressant effects in chronic unpredictable mild stress (CUMS) of BP were observed by behavioural indicators and 1H nuclear magnetic resonance (1H-NMR) and ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabonomics techniques combined with the related analysis platforms., Key Findings: BP could significantly improve the depressive behaviour of CUMS rats. Compared with the model group, body weight (P < 0.05), the number of crossing (P < 0.001) and rearing (P < 0.01) and sucrose preference rate (P < 0.01) were significantly enhanced, and the immobility time was shortened in the forced swimming test (P < 0.001) of the BP group. In metabonomics study, 35 depression-related metabolites were identified by 1H NMR and UHPLC-MS/MS metabonomics by comparing model and control groups. BP could significantly retrieve 17 depression-related metabolites. Thirteen depression-related metabolic pathways were found through Met-PA and BP could regulate seven metabolic pathways., Conclusions: BP herb pair had significantly antidepressant effect, which provides a basis for further finding drug targets., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Strontium vanadate nanoparticles embedded graphitic carbon nitride (g-C 3 N 4 /Sr 2 V 2 O 7 ) was facilely prepared in situ via a hydrothermal method. It was shown that the Sr 2 V 2 O 7 nanoparticles implanted into g-carbon nitride had a small size and high distribution. Importantly, compared with some other photocatalysts, the as-prepared g-C 3 N 4 /Sr 2 V 2 O 7 nanohybrid showed excellent photocatalytic activity for reduction of Cr(vi), and as high as 99% efficiency for Cr(vi) reduction (100 mg L -1 ) was reached within 8 min. Moreover, its activity was hardly changed after five cycles, demonstrating that the developed g-C 3 N 4 /Sr 2 V 2 O 7 nanohybrid was highly stable and promising an efficacious disposal of Cr(vi) in water. It was confirmed that the improved charge separation owing to more nitrogen vacancies in the hybrid was the main reason for the improved performance of the g-C 3 N 4 -Sr 2 V 2 O 7 nanohybrid., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Radix Bupleuri-Radix Paeoniae Alba (RB-RPA) is a classic herb pair, which is commonly used to treat depression by soothing "liver qi stagnation" in the clinic. However, little is yet known concerning the combination mechanism of Radix Bupleuri (RB) and Radix Paeoniae Alba (RPA), their bioactive forms in vivo and the regulatory effects on the organism. The present study aimed to elucidate the changes in multi-component pharmacokinetics (PK) behavior after the combination of RB and RPA by a high-resolution full-scan mode of UPLC-HRMS method (a total of 38 components PK profiles were obtained, of which 23 components come from RB and 15 components come from RPA). Moreover, the metabolomics approach was used to analyze the dynamic response of endogenous metabolites intervened by RB-RPA, and the correlation between concentration-time curves of 38 components from RB-RPA and the dynamic response profiles of endogenous metabolites was characterized by Pearson correlation analysis. The results demonstrated that the combination of RB and RPA could significantly improve the bioavailability of five components in RB, and six components in RPA. Besides, metabolomics results indicated that a total of 21 endogenous metabolites exhibited time-dependent changes in response to the RB-RPA administration, of which 12 endogenous metabolites were significantly increased, and nine endogenous metabolites were significantly decreased. Furthermore, correlation analysis results indicated that the components with significantly improved bioavailability after combination such as saikogenin F, saikogenin G, albiflorin, methyl gallate, paeonimetabolin II were significantly positively correlated with picolinic acid, a metabolite with neuroprotective effect; saikogenin F, saikogenin G were significantly positively correlated with itaconic acid, a endogenous metabolite with anti-inflammatory activity; and albiflorin, paeonimetabolin II were significantly positively correlated with α-linolenic acid, a metabolite with strong protective actions on brain functions. These results indicated that the combination of RB and RPA can enhance each other's neuroprotective and anti-inflammatory activities. In this study, A novel and efficient strategy has been developed to analyze the influence of the combination of RB and RPA in vivo behaviors by combining multi-component pharmacokinetics with metabolomics, which was contributed to clarifying the scientific connotation of herb-herb compatibility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Yin, Tian, Gao, Qin, Du and Zhou.)

Antimony has been listed as a critical pollutant in many countries because of its toxic effects on earth organisms. In this study, titanate nanosheets (TNS) were prepared with a high specific surface area by alkaline hydrothermal method. The adsorption mechanism and adsorption capacity of removing Sb(III) from aqueous solutions with TNS as an adsorbent were investigated for the first time. The FTIR and XPS analysis indicated that the interlayer sodium ions of TNS were responsible for Sb(III) adsorption. The batch experiments were conducted on solution pH, adsorbent dosage, initial concentration and reaction time. The results exhibited that when pH was 2, the removal rate was about 90% with the dosage of TNS was 0.1 g/L. The adsorption reaction was exceedingly rapid in the initial 5 min, and then the reaction was in equilibrium after about 30 min. The experimental data were better fitted with Langmuir isotherm model, and the maximum adsorption amount could attain 232.56 mg/g. The experiments showed that TNS had outstanding anti-interference performance to common cations. Therefore, TNS were considered to be an excellent material for removing Sb(III) from aqueous solutions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Liquiritin, a flavone derived from the medicine food homology plant liquorice, possesses neuroprotective. However, the neuroprotective mechanism is not clear. In this study, metabolomics based LC-MS was performed to discover the metabolite changes in PC12 cells treated with corticosterone-induced neurotoxicity after liquiritin treatment. A total of 30 metabolites were identified as differential metabolites. Among them, 11 metabolites were regulated by liquiritin, and involved in the D-glutamine and D-glutamate metabolism, and glutathione metabolism, etc. Based on the results of metabolomics, three cell signaling pathways related to these metabolic pathways were verified. The results showed that the ERK1/2-NF-κB pathway related to the D-glutamine and D-glutamate metabolism was attenuated by liquiritin via down-regulation phospho-ERK1/2, phospho-IκBα, phospho-NF-κB protein expression levels. Furthermore, the Nrf2-Keap1 pathway related to glutathione metabolism was activated by liquiritin via up-regulation Nrf2, Keap1, HO-1, NQO1 protein expression levels, and increased SOD, CAT, GSH-PX enzyme activity, thus exerting antioxidant activity. Additionally, liquiritin inhibited the mitochondrial apoptosis by decreasing the Ca 2+ concentration, improving MMP, up-regulating Bcl-2, and down-regulating Bax, cytochrome C, cleaved-Caspase-3 expression levels. These results suggest that the neuroprotective mechanisms of liquiritin are connected to the regulation of metabolic disorders, activation Nrf2/Keap1 pathway, attenuation ERK1/2/NF-κB pathway, and inhibition mitochondrial apoptosis pathway., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Puerarin has shown unique pharmacological effects on myocardial ischemia (MI). Changing the crystal form is an effective approach to improve the cardioprotective effects of puerarin. However, the mechanisms of the new crystal form of puerarin are unclear. In this study, an electrocardiogram, echocardiography, cardiac marker enzymatic activity, oxidative stress indices, and myocardial histology analysis of cardiac tissues were performed to evaluate the cardioprotective effects of the new crystal form of puerarin. Moreover, serum and cardiac tissue metabolomics based on nuclear magnetic resonance (NMR) were used to investigate the potential mechanism of the new crystal form. The results indicated that the new crystal form of puerarin (30 mg/kg) could improve oxidative stress indices, and these improvements were similar to those of the original crystal form of puerarin (120 mg/kg). The new crystal form of puerarin (30 mg/kg) could effectively improve the activities of cardiac marker enzymes, and the improvement effects were better than those of the original crystal form (120 mg/kg). Moreover, metabolomics analysis showed that amino acid metabolism, oxidative stress and energy metabolism were disturbed after MI and could be improved by puerarin. These results demonstrated that the new crystal form of puerarin was effective in treating MI.

A series of Ag-modified MOF/SOF heterostructured framework adsorbents (Ag-MSHC) with strong binding of iodine were prepared by anchoring silver nanoclusters on MOF/SOF heterostructured framework (MSHC). Morphological transformation process of six novel Ag-MSHC adsorbents can be realized by tailoring the molar ratio of Fe 3+ , TMA (1,3,5-Tricarboxybenzen) and MA (melamine), finally resulting in a combination of MOFs (metal-organic frameworks) and SOFs (supramolecular organic framework). Among six adsorbents, Ag-MSHC-6 exhibited an extremely strong affinity towards I - , whereas the maximum adsorption capacity of I - reaches 771.6 mg/g. An increased tendency of I - sorption occurred from Ag-MSHC-1 to Ag-MSCH-6 when the molar ratio of Fe 3+ gradually decreased because the content of Fe 3+ in topological structure of Ag-MSHC can hinder the incorporation of silver nanoclusters into Ag-MSHC and further influences the irreversible interactions between Ag 2 O and I - . Besides, FT-IR, XPS, TGA and SEM were used to discuss the microstructures and chemical composition of MSHC and Ag-MSHC, and we also performed batch adsorption experiments to demonstrate the iodine sorption performance and mechanism by Ag-MSHC. Taking advantage of this combination of MOFs and SOFs, high degree of doping of silver nanoclusters as well as its strong binding ability of iodine, Ag-MSHC can be considered as a superior adsorbent for radioactive iodine extraction., 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 © 2020 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Xiaoyaosan (XYS), composed of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae, is a valuable traditional Chinese medicine (TCM) which is used for the treatment of depression in China. In our previous experiments, we found that coniferyl ferulate (CF) was the main active constituent of Xiaoyaosan based on UPLC-PDA guided isolation technique. However, the antidepressant effect and mechanisms of CF is still unknown., Aim of the Study: In the current study, we aim to explore the possible mechanisms involved in the neuroprotective effect of CF in glutamate-injured PC12 cells, and further to confirm the anti-depressant effect of CF on the model of behavioral despair in vivo., Material and Methods: The model of glutamate-injured PC12 cells was employed to investigate the possible mechanisms involved in the neuroprotective effect of CF. The model of behavioral despair was carried out to examine the in vivo anti-depressant effect of CF., Results: The results showed that CF significantly attenuated the decrease of cell viability, the release of lactate dehydrogenase (LDH), and the increase of apoptosis rates induced by glutamate. CF could also suppress the influx of Ca 2+ and the elevation of p-NR2B, p-CaMK II, p-JNK, and p-p38 level induced by glutamate. Besides, CF could also inhibit the generation of reactive oxygen species (ROS), the decrease of SOD activity, the elevation of malondialdehyde (MDA) level, and suppress the loss of mitochondrial membrane potential (MMPs) and the activation Bcl-2/Bax mediated apoptotic pathways induced by glutamate. Furthermore, CF obviously decreased the immobility time in tail suspension test (TST) and forced swimming test (FST)., Conclusion: In conclusion, CF exert the indeed anti-depressant effect. The inhibition of NMDAR-CaMKII-MAPKs signaling pathway, oxidative stress, and mitochondrial apoptotic pathways were involved in the anti-depressant effect of CF., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine ( 8a ) showed the greatest inhibition of HCT116 cell activity with an IC 50 of 17.80 μg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.

Ethnopharmacological Relevance: In traditional Chinese medicine (TCM) theory, depression is considered to be "liver qi stagnation", and relieving "liver qi stagnation" is regarded as an effective method for treating depression. Xiaoyao San (XYS) is a well-known TCM formula for the treatment of depression by relieving "liver qi stagnation". This formula consists of Radix Paeoniae Alba (Paeonia lactiflora Pall.), Radix Bupleuri (Bupleurum chinense DC.), Poria (Poria cocos (Schw.) Wolf), Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Rhizoma Zingiberis Recens (Zingiber officinale Roscoe) and Herba Menthae Haplocalycis (Mentha haplocalyx Briq.)., Aim of the Study: Several studies have suggested that depression is associated with liver injury. XYS was a well-known TCM formula for the treatment of depression and liver stagnancy. However, it was still unknown whether the antidepressant effect of XYS is related to the pharmacological activity of hepatoprotection. The aim of this study was to elucidate the potential link between the antidepressant and hepatoprotective effect of XYS., Materials and Methods: A depression rat model was established by the CUMS (chronic unpredictable mild stress) procedure. The antidepressant effect of XYS was assessed by the behavioral indicators, and the hepatoprotective effect of XYS was evaluated through biochemical assays. 1 H-NMR and LC/MS-based liver metabolomics were performed to discover key metabolic pathways involved in the antidepressant and hepatoprotective effects of XYS. Further, the key pathway was validated using commercial kits., Results: The results demonstrated that XYS pretreatment could significantly improve the depressive symptom induced by CUMS. More importantly, the results demonstrated that liver injury was observed in the CUMS model rats, and XYS had a hepatoprotective effect by reducing the activities of AST and ALT in serum, increasing the levels of SOD and GSH-Px and reducing the contents of MDA, IL-6, and IL-1β in the liver. In addition, the NMR and LC/MS-based metabolomics results indicated that XYS improved 23 of the 35 perturbed potential liver biomarkers that were induced by CUMS. Among them, 9 biomarkers were significantly correlated with both depression and liver pathology, according to Pearson correlation analysis. Metabolic pathway analyses of these 9 biomarkers showed that glutamine and glutamate metabolism were the most important metabolic pathways. Furthermore, to verify glutamine and glutamate metabolism, the levels of glutamine and glutamate, and the activity of glutamine synthetase (GS) and glutaminase (GLS) were quantitatively determined in the liver by commercial kits, and these results were consistent with the metabolomics results., Conclusions: XYS could significantly improve the depressive and liver injury symptoms induced by CUMS. The metabolomics results indicate that the regulation of glutamine and glutamate metabolism to maintain the balance of ammonia and promote energy metabolism is a potential junction between the antidepressant and hepatoprotective effects of XYS., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Our previous work suggested that baicalein could delay senescence and improve cognitive dysfunction in senescence-accelerated mouse prone 8 (SAMP8). Although baicalein has shown therapeutical benefits in improving learning and memory impairment, the exact molecular mechanisms have not been fully understood. In the present work, transcriptomics was integrated with gene network analysis for revealing the potential mechanisms of baicalein in improving learning and memory in SAMP8 mice. The results showed that baicalein regulated fifty hub differently expressed genes (DEGs) that were enriched in eight signaling pathways. Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway was especially significant among them, therefore, the DEGs (Gh1, Il5, Il7, Il20rb, Prlr and Socs1) in JAK-STAT signaling pathway were verified by quantitative real-time PCR, and the key proteins (JAK2, p-JAK2, STAT1 and p-STAT1) and related proteins including β-amyloid peptide (Aβ 1-42 ) and receptor for advanced glycation end products (RAGE) were assayed by Western blot and enzyme-linked immunosorbent assay. Our results suggest that baicalein prevented the activation of JAK2/STAT1 signaling pathway and decreased the levels of Aβ 1-42 and RAGE in the cortex of SAMP8 mice. Taken together, our study unmasks the mechanism of baicalein on improving learning and memory impairment in SAMP8 mice, which is dependent upon the inhibition of Aβ 1-42 and RAGE/JAK2/STAT1 cascade., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) displays a promising antidepressant effects in patients with treatment-refractory depression; however, a clear consensus on underlying mechanisms is still enigmatic. Herein, we investigated the effects of MFB-DBS on anhedonic-like behavior using the Froot Loops® consumption in a chronic unpredictable mild stress (CUS) model of depression, biochemical estimation of peripheral and central inflammatory cytokines, stress hormone, and brain-derived neurotrophic factor (BDNF). Seven days of MFB-DBS significantly reversed the 42-day CUS-generated anhedonic-like phenotype (p < 0.02) indicated by an increase in Froot Loops® consumption. Gross locomotor activity and body weight remained unaffected across the different groups. A dramatic augmentation of adrenocorticotropic hormone levels was seen in the plasma and cerebrospinal fluid (CSF) samples of CUS rats, which significantly reduced following MFB-DBS treatment. However, C-reactive protein levels were found to be unaffected. Interestingly, decreased levels of BDNF in the CUS animals were augmented in the plasma, CSF, and hippocampus following MFB-DBS, but remained unaltered in the nucleus accumbens (NAc). While multiplex assay revealed no change in the neuronal levels of inflammatory cytokines including IL-1α, IL-4, IL-10, IL-12, IL-13, and IL-17 in the neuroanatomical framework of the hippocampus and NAc, increased levels of IL-1β, IL-2, IL-5, IL-6, IL-7, IL-18, TNF-α, and INF-γ were seen in these brain structures after CUS and were differentially modulated in the presence of MFB stimulation. Here, we show that there is dysregulation of BDNF and neuroimmune mediators in a stress-driven chronic depression model, and that chronic MFB-DBS has the potential to undo these aberrations.

In this study, we prepared a hydrothermal carbon-based supramolecular organic framework (HTC-MA-TMA) by grafting melamine and trimesic acid on hydrothermal carbon (HTC) for efficient removal of U (VI) from aqueous solutions. The nano-sized supramolecular organic framework (SOF) particles consisted of N-donor-containing melamine and O-donor-containing trimesic acid self-assembled through hydrogen bonds. Their large number of specific active sites acted as the immobilization center for capturing U (VI). Chemical modification facilitated the dispersion of the SOF particles on HTC, which was synthesized using a novel covalent/non-covalent bond strategy. The HTC-MA-TMA adsorbent exhibited exceptional U (VI) adsorption capacity (271.83 mg/g) because of the coordination interaction between UO 2 2+ and its ligands (amino, carboxyl and amide groups). The adsorption equilibrium was achieved within 30 min and followed a pseudo-second-order equation, suggesting the occurrence of a chemical adsorption process. Furthermore, the U (VI) ions adsorbed onto the HTC-MA-TMA adsorbent could be easily desorbed using 0.1 M HNO 3 solution. This regeneration caused no significant decrease in the sorption capacity of the adsorbent. These results suggest that advanced HTC-MA-TMA adsorbent can be applied in the nuclear-fuel industry for extracting U (VI) from radioactive wastewater., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Angelicae Sinensis Radix (AS), a well-known herb in traditional Chinese medicine (TCM), has been wildly used for replenishing the blood and promoting circulation, in Asia for thousands of years. It has been confirmed that AS also possesses the pharmacological activity of anti-depression. At the same time, recent studies suggested that depression is associated with anemia, and depression could be ameliorated via modulating the blood system. However, it is still unknown whether the anti-depression effect of AS is related to its pharmacological activity of modulating the blood system. In the current study, hematological examination and metabonomic techniques were performed to explore potential anti-depression mechanisms of AS, related to the function of modulating the blood system in a chronic unpredictable mild stress (CUMS) model. The results demonstrated that AS could significantly improve CUMS-induced depressive symptom, hematological anomalies, and hypoxia symptoms. The analysis of metabonomics demonstrated that 26 potential biomarkers in depression could be regulated by the administration of AS. Among them, eight biomarkers participate in the metabolic pathways of amino acid and sphingolipid, and energy metabolism could also be regulated in an anemia model through the administration of AS, as reported in previous literatures. Further results proved that AS modulated energy metabolism in depression through the inhibition of the expression of pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK-1) and lactate dehydrogenase A (LDHA). These results suggested that the modulation of the blood system was involved in the anti-depression effect of AS. The mechanism may be associated with the promotion of the body's energy metabolism, the stabilization of cell membranes, the promotion of serum protein synthesis, and the enhancement of immunity.

Scutellaria baicalensis Georgi (SBG), a traditional Chinese herb, has attracted considerable attention for its wide range of pharmacological activities. This study aimed to investigate the intervention effects of SBG ethanol extract on aging rats induced by D-galactose (D-gal) and to explore potential mechanisms by serum and liver metabolic profiles. The aging rats were induced by the D-gal (100 mg/kg) for 10 weeks continuously with subcutaneous injection, while the control rats received physiological saline. Two other groups of rats were administered with 100 mg/kg/day and 200 mg/kg/day of SBG by oral route following D-gal injections. The abilities of spatial and learning memory were evaluated by open-field test and Morris water maze test. Then, some biochemical indexes related to cognitive ability and aging were measured. Histopathological feature in hippocampal region was observed by Hematoxylin and eosin (HE) staining. The changes of metabolic profiles were evaluated using proton nuclear magnetic resonance ( 1 H NMR) spectroscopy coupled with multivariate data analysis. Results showed that SBG could significantly improve the learning and memory functions, reducing oxidative damage and histological abnormalities of hippocampus neurons. In addition, significant differences in the metabolic profiles were observed both in serum and liver between the model group and the control group. After the treatment using SBG, the levels of these metabolites are significantly changed back to their similar levels in the control group. These metabolic changes are related to the disturbance in amino acid metabolism, glycometabolism and choline metabolism. Hence, SBG may have the potential to improve neurodegeneration and provide brain protection. Graphical abstract A 1 H NMR-based metabonomic study was conducted to provide a global view of metabolites related to D-gal induced aging rats and assess the holistic efficacy of Scutellaria baicalensis Georgi.

Licorice, an edible and officinal plant material, has attracted considerable attention for its wide range of pharmacological activities. Our previous study showed that licorice can ameliorate cognitive damage and improve oxidative stress and apoptosis in aging rats induced by d-galactose (d-gal). In this study, in order to further explore the changes of the metabolic profile during the aging process and the antiaging mechanism of licorice, the 1H NMR-based metabolomics approach was used to analyze serum and urine samples and identify a potential biomarker in d-gal induced aging rats. The results revealed that the taurine metabolic pathway was significantly correlated with the ageing process in d-gal induced rats. Furthermore, the taurine contents were significantly decreased in both the serum and urine samples of aging rats compared with the controls. At the same time, the levels of cysteine dioxygenase type I (CDO1), cysteine sulfinic acid decarboxylase (CSAD) and glutamate decarboxylase type I (GAD1), which are the key enzymes affecting the synthesis reactions, were decreased in aging rats compared with the controls. After licorice administration, the levels of taurine, CDO1 and CSAD were all significantly increased. These findings firstly demonstrated that the regulation of the taurine metabolic pathway is involved in the anti-aging effect of licorice in d-gal induced aging rats.

Baicalein, a flavonoid derived from the roots of Scutellariae baicalensis Georgi, has shown health benefits for an array of human diseases including dementia. The senescence-accelerated mouse prone 8 (SAMP8) strain is extensively used as a senile dementia model. To further investigate the effects of baicalein in SAMP8 mice, behavioral testing, biochemical detection, and gut microbiota analysis were performed. The results demonstrated that treatment with baicalein ameliorated the senescence status of the SAMP8 mice, as manifested by reducing the grading score of senescence. Additionally, baicalein improved the cognitive functions of the SAMP8 mice, including spatial learning and memory abilities, object recognition memory, and olfactory memory. Furthermore, baicalein significantly inhibited the release of proinflammatory cytokines such as interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) in the brain cortex of SAMP8 mice. Gut microbiota analysis revealed that treatment with baicalein markedly altered the abundance of six genera in SAMP8 mice. Correlation analysis indicated that the abundances of Mucispirillum, Bacteroides, and Sutterella were negatively correlated with cognitive abilities and that Christensenellaceae was positively correlated with cognition. Furthermore, the abundance of Christensenellaceae was negatively correlated with the levels of IL-6 and TNF-α, while [ Prevotella] was positively correlated with the levels of IL-1β and IL-6. In addition, Mucispirillum and Bacteroides were positively correlated with the level of IL-6 in the brain cortex. These data indicated that baicalein ameliorates senescence status and improves cognitive function in SAMP8 mice and that this effect might be attributable to suppression of cortical proinflammatory cytokines and modulation of the intestinal microbiome.

The Kerker preconditioner, based on the dielectric function of homogeneous electron gas, is designed to accelerate the self-consistent field (SCF) iteration in the density functional theory calculations. However, a question still remains regarding its applicability to the inhomogeneous systems. We develop a modified Kerker preconditioning scheme which captures the long-range screening behavior of inhomogeneous systems and thus improves the SCF convergence. The effectiveness and efficiency is shown by the tests on long-z slabs of metals, insulators, and metal-insulator contacts. For situations without a priori knowledge of the system, we design the a posteriori indicator to monitor if the preconditioner has suppressed charge sloshing during the iterations. Based on the a posteriori indicator, we demonstrate two schemes of the self-adaptive configuration for the SCF iteration.

Background: Aging is a complex process accompanied with the decline of the different physiological functions. Numerous differentially expressed genes (DEGs) have been found in the aging brain of senescence-accelerated mouse P8 (SAMP8), however, it was challenging to screen out the crucial ones., Objective: This study aimed to explore the crucial genes and pathways in aging brain of SAMP8 mice, which would be beneficial for understanding the pathogenesis of brain aging., Methods: Firstly, 430 genes that are differentially expressed in SAMP8 mice versus SAMR1 mice were obtained from 9 gene expression studies, and gene-gene network was constructed. Clustering analysis and topological analysis were used to single out the hub genes from this network. Secondly, pathway enrichment analysis was utilized to identify the key pathways from the 430 DEGs, and the DEGs in key pathways were considered as functional genes. Thirdly, the inner-network between hub genes and functional genes was constructed, and the key genes were predicted. Parts of the key genes were experimentally verified by quantitative real-time PCR (qRT-PCR), and the associated transcription factors (TFs) were predicted., Results: Our results revealed that 12 crucial genes might affect brain aging, including Trp53, Bcl2, Tnf, Casp9, Fos, Il6, Ptgs2, Il1b, Bdnf, Cdkn1a, Pik3c3, Rps6ka1, among which Casp9, Fos, Ptgs2, Cdkn1a, Pik3c3, and Rps6ka1 had been verified by qRT-PCR in 10-moth-old SAMP8 mice. Five functional groups including mitogen-activated protein kinase (MAPK) signaling pathway, neurotrophin signaling pathway, Hepatitis B, Alzheimer's disease and Oxytocin signaling pathway were significantly changed during aging process in SAMP8 mice. Two key transcription factors of c-Fos and C/EBPbeta were predicted by constructing a TF-target gene network., Conclusion: These putative genes and pathways are closely related to brain senescence and our results would gain new insight into the pathogenesis of brain aging., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Gold-mediated exfoliation of ultralarge optoelectronically perfect monolayers with lateral dimensions up to ≈500 μm is reported. Electrical, optical, and X-ray photo-electron spectroscopy characterization show that the quality of the gold-exfoliated flakes is similar to that of tape-exfoliated flakes. Large-area flakes allow manufacturing of large-area mono-layer transition metal dichalcogenide electronics., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Seven phthalides, including a new dimeric one named tokinolide C (7), were isolated from Angelicae Sinensis Radix and characterized. The structures of these compounds were elucidated on the basis of comprehensive analysis of spectroscopic data and comparison with literature data. All of the compounds were evaluated for their cytotoxic activities against the A549, HCT-8, and HepG2 cancer cell lines. Riligustilide (4) showed cytotoxicity against three cancer cell lines, with IC50 values of 13.82, 6.79, and 7.92 μM, respectively. Tokinolide A (6) and tokinolide C (6) exerted low cytotoxicity in these cancer cell lines, while the remaining compounds were inactive. Flow cytometry analysis was employed to evaluate the possible mechanism of cytotoxic action of riligustilide (4). We observed that compound 4 was able to arrest the cell cycle in the G1, S phases and induce apoptosis in a time-dependent manner in HCT-8 cell lines. In addition, these compounds were evaluated for neuroprotective effect against SH-SY5Y cells injured by glutamate. The result showed that ligustilide (1), Z-butylidenephthalide (3) and tokinolide A (6) exhibited significant neuroprotective effects.

Ethnopharmacological Relevance: Xiaoyaosan (XYS), a well-known formula for relieving depression, was originated from the book of "Taiping Huimin Heji Jufang" in Song Dynasty (960-1127 AD), composed of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae with dose proportion of 6:6:6:6:6:3:2:2. It is commonly used for the treatment of depression-related syndromes in China. In the formula, Radix Bupleuri usually serves as the principal drug, Radix Angelicae Sinensis and Radix Paeoniae Alba serve as the ministerial drugs, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae and Rhizoma Zingiberis Recens serve as adjunctive drugs, Radix Glycyrrhizae serves as messenger drug, they coordinate with each other and enhance the effect of the formula. In our previous experiments, the antidepressant effect of XYS was revealed. However, the antidepressant part (or component) of this prescription was still obscure., Materials and Methods: An experimental despair animal model: the mice tail suspension test (TST) was used to evaluate the antidepressant activity of XYS and its fractions. GC-MS method was developed to identify the volatile components and determine 4 major volatile components in active fraction., Results: In the TST test, the effect of a low polar fraction (XY-EA) was superior to other fractions of XYS. 13 volatile compounds in the XY-EA were identified on the basis of standards, isolation and structural determination in our laboratory, NIST 05 database and literature data. The content of 4 major volatile compounds in XY-EA which is 6.703%., Conclusions: The petroleum ether fraction (XY-EA) appears to be the active fraction of XYS. 4 major components Z-ligustilide, palmitic acid, atractylenolide I, and atractylenolide II may be the antidepressant active compounds., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Xiaoyaosan (XYS), composed of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae, is a valuable traditional Chinese medicine (TCM) which is used for the treatment of depression in China. In the formula, Radix Bupleuri usually serves as the principal drug, Radix Angelicae Sinensis and Radix Paeoniae Alba serve as the ministerial drugs, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae and Rhizoma Zingiberis Recens serve as adjunctive drugs, Radix Glycyrrhizae serves as messenger drug, they coordinate with each other and enhance the effect of the formula. In our previous experiments, the antidepressant effect of XYS was revealed. However, the antidepressant part (or component) of this prescription was still obscure. We divided the XYS into five different polar fractions, and explored the antidepressant activity of five different polar fractions to identify the active fraction., Materials and Methods: Behavior research and metabonomics method based on (1)H NMR were used for efficacy study of different fractions in chronic unpredictable mild stress (CUMS) model of depression. Rats were divided into 8 groups and drugs were administered during the 21 days model building period. The urine samples of rats were collected overnight (12h) on 21 day and the metabolic profiling of the urine was measured using NMR. Multivariate analysis was also utilized to evaluate the active fraction of XYS., Results: In the behavior research, there were significant difference between the lipophilic fraction group (XY-A) and the model group. In addition, with pattern recognition analysis of urinary metabolites, the results showed a clear separation of the model group and control group, while XY-A group was much closer to the control group in the OSC-PLS score plot. Seven endogenous metabolites contributing to the separation of the model group and control group were detected, while XY-A group regulated the 5 perturbed metabolites showing a tendency of recovering to control group., Conclusions: The present work suggested that petroleum ether fraction was the most effective fraction, implying that lipophilic components contribute to the antidepressant effect of XYS., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacology: Xiaoyaosan (XYS), a famous Chinese prescription, composed of Radix Bupleuri (Bupleurum chinense DC.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Radix Paeoniae Alba (Paeonia lactiflora Pall.), Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), Poria (Poria cocos (Schw.) Wolf), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Herba Menthae (Mentha haplocalyx Briq.), and Rhizoma Zingiberis Recens (Zingiber officinale Rosc.), has been widely used in the clinic for treating mental disorders. Behavior and biochemical analyses indicate XYS has obvious anti-depression activity. However, there is no report on the effects of XYS using a metabolomics approach., Aim of the Study: Depression is a prevalent complex psychiatric disorder and its pathophysiological mechanism is not yet well understood. This paper was designed to study metabonomic characters of the depression induced by chronic unpredictable mild stress (CUMS) and the therapeutic effects of XYS, classic traditional Chinese medicine (TCM) in treating the depression., Material and Methods: A plasma metabonomics method based on gas chromatography/mass spectrometry (GC/MS) was developed. Principal component analysis (PCA) was utilized to classify and reveal the differences between the model group and control group. In turns, the concentration of these differences was analyzed with t-test to determine whether XYS was possible to influence the metabolic pattern induced by CUMS., Results: The significant difference in metabolic profiling was observed from model group compared with drug-dose group by using the PCA, indicating the recovery effect of XYS on CUMS rats. Some significantly changed metabolites like glycine, glucose and hexadecanoic acid have been identified. These biochemical changes are related to the disturbance in amino acid metabolism, energy metabolism and glycometabolism, which are helpful to further understand the CUMS and the therapeutic mechanism of XYS., Conclusions: Metabonomic approach is helpful to further understanding the pathophysiology of depression and assisting in clinical diagnosis of depression and is also a valuable tool for studying the essence of Chinese medicine's syndrome theory and therapeutic effect mechanism of TCM., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacology: Xiaoyaosan, a famous Chinese prescription, composed of Poria (Poria cocos (Schw.) Wolf), Radix Paeoniae Alba (Paeonia lactiflora Pall.), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Radix Bupleuri (Bupleurum chinense DC.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), Herba Menthae (Mentha haplocalyx Briq.), and Rhizoma Zingiberis Recens (Zingiber officinale Rosc.), has been widely used in the clinic for treating mental disorders. Behavior and biochemical analyses indicate xiaoyaosan has obvious anti-depression activity. However, there is no report on the effects of xiaoyaosan using a metabolomics approach., Aim of the Study: A urinary metabolomics method was applied to evaluate the efficacy of xiaoyaosan on rat model of chronic unpredictable mild stress., Material and Methods: Rats were divided into 6 groups and drugs were administered during the 21-day model building period. Urine was measured using GC-MS, processed with XCMS and Microsoft Excel and analyzed by SIMCA-P and SPASS software. Variable importance in projection statistics and loading plot were used to find biomarker ions., Results: Clear separation between model and each drug group was achieved. High dose group of xiaoyaosan was much closer to control group than middle dose group and amitriptyline group. The time-dependent recovery tendency in high dose group was obtained., Conclusions: In term of anti-depression effect, high dose xiaoyaosan was the most effective and amitriptyline equaled middle dose xiaoyaosan as shown by metabolomics strategy and behavior tests. Some common and characteristic metabolites on the anti-depression of xiaoyaosan and amitriptyline were obtained. The work showed metabolomics is a valuable tool in studying the efficacy and potential biomarkers of therapeutic effect of complex prescriptions., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Seven new steroidal glycosides (amplexicosides A (4), B (7), C (8), D (9), E (10), F (11), and G (12)), along with six known compounds (cynatratoside A (1), tylophoside A (2), cynatratoside B (3), glaucogenin A (5), glaucoside A (6), and hancoside A (13)) were isolated from the 95% ethanol extract of the roots of Cynanchum amplexicaule (Sieb. et Zucc.). Their structures were determined based on spectral and chemical evidence. Compound 12 has a 14, 15-secopregnane-type skeleton aglycone, which has not been reported in literature.