Ferroptosis plays a crucial role in lung cell damage caused by ventilation stretch.

Mechanical ventilation is an essential respiratory support in acute respiratory distress syndrome and intensive care cases. However, it is possible to cause ventilator-induced lung damage (VILI). In this work, we used a microfluidic device to provide a mechanical ventilation with cyclic stretch (30% total area change rate and 15 cycles per min) and oxygen (air) flux applied by a controlled pressured airflow. Compared to static control, the ventilation stretch resulted in significant death of A549 cells accompanied by increased lipid peroxidation, mitochondrial reactive oxygen species (ROS) production, and ferrous ion accumulation, while by decreased protein expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) proteins, as well as ratio of reduced-to-oxidized glutathione. The resulted A549 cell death could be alleviated by two ferroptosis inhibitors, deferoxamine and ferrostatin-1. These similar phenomena also occurred in other three types of human lung cells, such as primary alveolar type II epithelial cells, primary alveolar microvascular endothelial cells, and bronchial epithelial cell line. From the A549 RNA sequence analysis, the gene ontology (GO) based on 85 ferroptosis-related genes (FRGs) indicated that several iron homeostasis-related biological processes and molecular functions were involved in the ventilation-stretch-induced cell death, while the gene set enrichment analysis (GSEA) based on 2901 differentially expressed genes (DEGs) showed that glutathione metabolism was significantly suppressed. Finally, solute carrier family 39 member 14 (SLC39A14), a transporter of uptake extracellular divalent metal ion, was selected to be knocked down to verify its role in the ventilation-stretch-induced death of A549. Our results suggest that ferroptosis may be an alternative pathway for VILI, but it needs to be confirmed by further animal experiments and clinical data.

Extracranial metastasis of glioblastoma: A case report and literature review.

INTRODUCTION: Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. Extracranial metastasis is rare, accounting for only 0.4 %-0.5 % of all GBM patients. The pathways and mechanisms involved are still unclear. CASE PRESENTATION: We reported a rare case of GBM with multiple bone metastases, highly suspected of abdominal metastasis. This 20 year old woman underwent surgery in March 2017 and underwent postoperative radiotherapy and chemotherapy. In July 2018, she underwent a second surgery due to intracranial recurrence and also underwent radiotherapy and chemotherapy after the surgery. She experienced pain in the lumbosacral region in May 2019, abdominal magnetic resonance imaging (MRI) showed metastases to the ilium, sacrum, and multiple lumbar vertebrae. In August 2019, a lump was discovered at the sternum and biopsy was performed, pathological examination confirmed it as GBM. During this period, the patient's condition was briefly controlled after receiving palliative radiotherapy, chemotherapy, and targeted treatment. Surprisingly, the patient later developed highly suspected malignant ascites, and further anti-tumor treatment was refused. She died 7 months after diagnosis of extracranial metastases. CLINICAL DISCUSSION: This patient with GBM had multiple bone metastases and highly suspected abdominal metastasis after two operations. Chemotherapy, radiotherapy and Targeted therapy extend the survival period and improve the quality of life. CONCLUSION: We believe that the patient's extracranial metastases may have occurred through blood. Young "long-term survivors" who have undergone surgery seem to have a higher risk of extracranial metastasis. Timely detection and early treatment can improve the overall quality of life of the patient.

Erratum: "Microfluidic-to-macrofluidic: A simple in vitro model of atherosclerosis induced by fluidic stimulation" [Biomicrofluidics 17, 044106 (2023)].

[This corrects the article DOI: 10.1063/5.0155267.].

Microfluidic-to-macrofluidic: A simple in vitro model of atherosclerosis induced by fluidic stimulation.

Atherosclerosis is the narrowing of the arteries due to the formation of fatty plaques, which is the main cause of myocardial infarction and stroke. It is important to develop an in vitro model that can combine multiple-type cell co-culture, vessel wall-like structure, and fluid condition to simulate the processes of atherosclerosis. Herein, we used a simple microfluidic chip made of three polydimethylsiloxane layers to co-culture endothelial and smooth muscle cells in a flat rectangular microchannel. After being connected with a circulating culture medium driven by a peristaltic pump, the flat microchannel was deformed to a tunnel-like macrochannel. The fluid pressure and shear stress applied on the cells in the deformed macrochannel can be varied by adjusting the circulating flow rate and the thickness of the middle layer. Under three levels of the pressure (65, 131, and 196 mm Hg) or shear stress (0.99, 4.78, and 24 dyne/cm2) conditions, a series of atherosclerosis-related events, including endothelial cell junction, pro-inflammatory cytokine secretion, monocyte adhesion, and lipid accumulation, were investigated. The atherosclerosis-related results showed that the medium pressure or shear stress exhibited a relatively weak pro-atherosclerotic effect in a V-shaped trend. To demonstrate the potential in drug screen, the effects of three well-known anti-atherosclerotic drugs (atorvastatin, tetramethylpyrazine, and high-density lipoprotein) on the lipid accumulation and pro-inflammatory cytokine secretion were evaluated under a strong pro-atherosclerotic fluid condition (65 mm Hg, 0.99 dyne/cm2). This in vitro model of atherosclerosis has shown great potential in drug screen application.

Digital Image Restoration Based on Multicontour Batch Scanning.

In order to explore the problem of digital image restoration, the authors propose a research on digital image restoration based on multicontour batch scanning. This method recommends key technical problems and solutions based on information represented by multicontour batch scans, exploring research in digital image restoration. Research has shown that the research on digital image restoration based on multicontour batch scanning is about 40% more efficient than traditional methods. Aiming at the new application of digital image inpainting, the application of image inpainting in image compression is studied in depth, and the technical principles of image inpainting and image compression are complemented.

Anti-influenza virus activity of the REV-ERBα agonist SR9009 and related analogues.

REV-ERBα is a member of the nuclear receptor superfamily of transcription factors that aids in the regulation of many diseases. However, the prospect of using REV-ERBα for anti-influenza virus treatment remains poorly described, and there is an urgent need to develop effective anti-influenza agents due to the emergence of drug-resistant influenza viruses. In this study, eight SR9009 analogues were designed, synthesized, and evaluated for their biological activities against multiple influenza virus strains (H1N1, H3N2, adamantane- and oseltamivir-resistant H1N1 and influenza B virus), using ribavirin as the positive control. SR9009 and its analogues showed low micromolar or submicromolar EC50 values and exhibited modestly improved antiviral potency compared to that of ribavirin. In particular, compound 5a possessed the most potent inhibitory activity (EC50 = 0.471, 0.644, 1.644, 0.712 and 0.661 µM for A/PR/8/34, A/WSN/33, A/Wisconsin/67/2005, B/Yamagata/16/88 and Hebei/SWL1/2006, respectively). Cotransfection assays showed that all synthesized derivatives efficaciously suppressed transcription driven by the Bmal1 promoter. Mechanistic study results indicated that 5a efficiently inhibited IAV replication and interfered with the ealry stage of influenza virus life cycle. In addition, we found that 5a upregulated the key antiviral interferon-stimulated genes MxA, OAS2 and CH25H. Further in-depth transcriptome analysis revealed a series of upregulated genes that may contribute to the antiviral activities of 5a. These findings may provide an important direction for the development of new host-targeted broad-spectrum antiviral agents.

Dose Optimization of Anxiolytic Compounds Group in Valeriana jatamansi Jones and Mechanism Exploration by Integrating Network Pharmacology and Metabolomics Analysis.

Anxiety disorder impacts the quality of life of the patients. The 95% ethanol extract of rhizomes and roots of Valeriana jatamansi Jones (Zhi zhu xiang, ZZX) has previously been shown to be effective for the treatment of anxiety disorder. In this study, the dose ratio of each component of the anxiolytic compounds group (ACG) in a 95% ethanol extract of ZZX was optimized by a uniform design experiment and mathematical modeling. The anxiolytic effect of ACG was verified by behavioral experiments and biochemical index measurement. Network pharmacology was used to determine potential action targets, as well as predict biological processes and signaling pathways, which were then verified by molecular docking analysis. Metabolomics was then used to screen and analyze metabolites in the rat hippocampus before and after the administration of ZZX-ACG. Finally, the results of metabolomics and network pharmacology were integrated to clarify the anti-anxiety mechanism of the ACG. The optimal dose ratio of ACG in 95% ethanol extract of ZZX was obtained, and our results suggest that ACG may regulate ALB, AKT1, PTGS2, CYP3A4, ESR1, CASP3, CYP2B6, EGFR, SRC, MMP9, IGF1, and MAPK8, as well as the prolactin signaling pathway, estrogen signaling pathway, and arachidonic acid metabolism pathway, thus affecting the brain neurotransmitters and HPA axis hormone levels to play an anxiolytic role, directly or indirectly.

[Spectrum-effect relationship of the blood-activating efficacy of Notoginseng Radix et Rhizoma].

This study aims to establish the high-performance liquid chromatography(HPLC) fingerprints of different batches of Notoginseng Radix et Rhizoma, determine their pharmacodynamic indexes of promoting blood circulation, and explore the spectrum-effect relationship between the chemical components of Notoginseng Radix et Rhizoma and the efficacy of promoting blood circulation. Firstly, the HPLC fingerprints of different batches of Notoginseng Radix et Rhizoma were established. Then, the pharmacodynamic indexes were determined after the capillary coagulation experiment and the cerebral ischemia-reperfusion in rats, including capillary coagulation time, percentage of cerebral ischemic area, cerebral water loss rate, and brain-body index. Afterward, the partial least-squares method was used to explore the spectrum-effect relationship between the chemical components of Notoginseng Radix et Rhizoma and the pharmacodynamic indexes. The results showed that this study successfully established the HPLC fingerprints of different batches of Notoginseng Radix et Rhizoma, found 23 common peaks, and identified 12 of them, all of which were saponins. The method was proved stable and reliable. Both the capillary coagulation experiment and the middle cerebral artery occlusion(MCAO)-induced cerebral ischemia-reperfusion experiment on rats revealed that there were obvious differences in the pharmacodynamic indexes of different batches of Notoginseng Radix et Rhizoma. The relationships between 23 common components of Notoginseng Radix et Rhizoma in different batches and the pharmacodynamic indexes were discussed by means of spectrum-effect correlation analysis, of which 17 components had positive effects while 6 components had negative effects on the pharmacodynamic indexes. This study provides a certain reference basis for the clinical rational use and quality control of Notoginseng Radix et Rhizoma.

Application of a fugacity model to estimate emissions and environmental fate of ship stack PAHs in Shanghai, China.

The understandings of environmental activities and regional inventory of ship stack PAHs are very limited in Shanghai due, in part, to the lack of source-segregated analysis. To address this, measured PAHs in organic film on ship surfaces were employed to reconstruct concentrations in various compartments through a fugacity model to investigate the level, transport, fate and annual emission of ship stack PAHs in Shanghai. The results revealed that ship stack PAHs results in 11.2-181 ng L-1 and 71.0-1710 ng g-1 in water and sediment of Shanghai, respectively. After being released into air, ship stack PAHs mainly concentrated in organic films and sediments while sunk in water and sediment. Crucial mass transfer pathways include deposition of airborne and sediment PAHs. The mass loss of ship stack PAHs was primarily through air advection, followed by degradation in sediment. The ship emissions (53.7 tons annually) accounted for approximate one tenth of the regional total in Shanghai (in 2017). Additionally, shipping was estimated to release 127 tons of PAHs annually into the Shanghai section of Yangtze River. Our results suggest our fugacity-based approach can be used to estimate the regional emissions and inventory of ship stack PAHs in the surrounding environment.

Polycyclic aromatic hydrocarbon contamination along roads based on levels on vehicle window films.

Vehicular emissions are known to be major contributors of airborne polycyclic aromatic hydrocarbons (PAHs) in cities. In order to assess the long-term contamination of PAHs along roads, we collected organic films from vehicle windows (26 private cars and 4 buses, in Shanghai, China) and used mathematical models to convert the film-bound PAH concentrations to the airborne PAH concentrations. The field measurements of airborne PAHs revealed that the partitioning and Level III fugacity model was suitable to estimate the airborne concentrations of high and low volatile PAHs (expect for naphthalene), respectively. The total airborne PAH concentrations along roads in Shanghai ranged from 0.83 to 3.37 µg m-3 and the incremental lifetime cancer risks (ILCRtotal) by exposure to PAHs along roads were greater than the USEPA lower guideline of 10-6, indicating non-negligible carcinogenic risks to drivers and passengers, especially via ingestion processes. This study provided a practicable method to investigate long-term air contamination of PAHs in vehicles and along roads based on film-bound PAH on vehicle windows. In addition, it was also possible to investigate the health risk in vehicles as a result of exposure to PAHs. Comparisons of PAHs between roads and shipping lanes also facilitated the delineation of vehicular and shipping PAH inventories. A capsule that summarizes the main finding of the work: Investigating film-bound PAH on vehicle windows is a practicable pathway to investigate the long-term contamination of PAHs in vehicles and along roads. This method can not only simplify the sampling processes, but the model calculations. The results also enabled investigations into ILCR in vehicles and specified source apportionment of traffic PAHs.

Reversible Information of Encrypted Image Based on Feature Difference Detection and Wavelet Transform.

Aiming at the shortcomings of the existing lossless digital watermarking algorithm based on frequency domain in reversibility and embedding capacity, this study proposes a lossless digital image watermarking algorithm based on fractional wavelet transform, which is used for large-capacity reversible information hiding of images. First, the image is transformed by LeGall5/3 fractional wavelet, and then, the watermark is embedded in the high-frequency subband by the histogram shift method. In order to obtain maximum embedding capacity and reduce image distortion, the methods of selecting embedding parameters and stopping parameters are proposed, respectively. At the same time, in order to prevent overflow and reduce additional information, a new method of generating position map is proposed. The experimental results show that Lena is the result of multilayer embedding based on the algorithm in this study. In order to better observe the distortion phenomenon and enlarge the image, the Lena test image is the watermark image obtained after two and three layers of embedding, and its embedding capacity can be 2.7 bpp. It is proved that wavelet transform is suitable for encrypted images to implement covert communication.

Discovery and proteomics analysis of effective compounds in Valeriana jatamansi jones for the treatment of anxiety.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhizhu Xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. However, there have been few investigations to clarify the compounds in ZZX for the treatment of anxiety. AIM OF THE STUDY: Our previous study has identified five anti-anxiety components, including hesperidin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C and chlorogenic acid, from extract of ZZX. In order to find the optimal combination and the underlying mechanism of these five components in the treatment of anxiety disorder, researches were designed based on uniform design method and proteomic technology. MATERIALS AND METHODS: The samples with different proportion and content of the five active components were arranged by uniform design method. Then a mathematical model was formulated using partial least square method and stepwise regression analysis. Moreover, the empty bottle stress-induced anxiety rat model was established, and the anti-anxiety effect was recorded by the unconditioned reflex elevated maze test and the open field test. In addition, the isobaric tags for relative and absolute quantitation (iTRAQ) technique, along with the multidimensional liquid chromatography and high-resolution mass spectrometry were applied in proteomic study. At last, the result of proteomic analysis was further confirmed by Western blot. RESULTS: The optimal combination of the components from the extract of ZZX was 1.153 mg/kg hesperidin, 2.197 mg/kg Isochlorogenic acid A, 0.699 mg/kg Isochlorogenic acid B and 1.249 mg/kg Chlorogenic acid. Total 6818 proteins were identified using proteomic analysis and 80 differentially expressed proteins were used for further bioinformatic analysis. These proteins were involved in the neuroactive ligand-receptor interaction, protein digestion and absorption, cholesterol metabolism, Chagas disease, and AGE/RAGE signaling pathway. CONCLUSIONS: The composition and proportion of anti-anxiety components in extract of ZZX was disclosed, and there was an anti-anxiety effect for the combined components of flavonoids and phenolic acids. Through proteomic analysis and Western blot, it was found that the effective components of extract of ZZX can exert synergistic anti-anxiety effects via the regulation of multi-signaling pathways. These findings could provide a preliminary research basis for the development of new low-toxic, efficient, stable and controllable anti-anxiety drugs.

Anxiolytic Effect of Alcohol-Water Extracted Suanzaoren-Wuweizi Herb-Pair by Regulating ECS-BDNF-ERK Signaling Pathway Expression in Acute Restraint Stress Male Rats.

Herb-pairs are the basic units of composition in Chinese herbal formulae, where the bridge linking Chinese medicine and prescription consists of two Chinese medicine herbs. The Suanzaoren-Wuweizi herb-pair (SWHP) is commonly used as a sedative or tranquilizer. SWHP has been demonstrated to exert an antianxiety effect in animal models of anxiety. However, little information about its mechanism is available and the effects of SWHP have not been investigated. This study examined the effects of SWHP on ameliorating anxiety-like behaviors by regulating endocannabinoids system (ECS)-brain-derived neurotrophic factor (BDNF)-extracellular regulated protein kinases (ERK) signaling pathway expression, induced by restraint stress (RS) procedures. The antianxiety effects of SWHP on RS rats were then examined through the open-field test (OF) and the elevated plus maze test (EPM). The concentration of BNDF, ERK1/2, p-ERK1/2, cAMP-response element binding protein (CREB), and p-CREB expression in the prefrontal cortex and hippocampus of the rats was then measured by western blot. The number of positive cells of CB1 and CB2 in the rats' hippocampus CA1 region was measured by immunohistochemistry. These results gave compelling evidence that SWHP could modify anxiety-like behaviors of RS rats through regulation of the ECS-BDNF-ERK signaling pathway. Our study demonstrated that SWHP improved anxiety-like behaviors in RS rat models by regulating the ECS-BDNF-ERK signaling pathway. The findings indicate that SWHP may have a therapeutic application in the RS model of anxiety disorder, which proposes a potential new direction for research into anxiety disorders regarding mechanisms and the development of novel antianxiety drugs.

Polycyclic aromatic hydrocarbon contaminations along shipping lanes and implications of seafarer exposure: Based on PAHs in ship surface films and a film-air-water fugacity model.

Polycyclic aromatic hydrocarbons (PAHs) are one of the most toxic compounds in ship tailpipe exhausts. The long-term contamination of PAHs along shipping lanes and ports is difficult to assess using conventional methods such as AIS-EFs-data based (AIS, Automatic identification system; EFs, emission factors) or field sampling methods. To address this, we collected the organic films on ship surfaces and used a modified film-air-water fugacity model to convert the film-bound concentrations to the airborne (gaseous plus particulate) concentrations. Not surprisingly, concentrations of PAHs on organic films on ship surfaces were greater than those measured on films on residential buildings. The airborne total PAH concentrations along shipping lanes in Yangtze River Delta area ranged from 63.3-325 ng m-3, which were in the same order of magnitude to those in Beijing during haze days. The incremental lifetime cancer risks by exposure to PAHs in ship indoor air were higher than the US EPA lower guideline, indicating considerable carcinogenic risks to seafarers. Our study proposes an alternative method to estimate the long-term contaminations of PAHs along shipping lanes and highlights a notable health risk to seafarers.

Real-time monitoring of multicomponent reactive dye adsorption on cotton fabrics by Raman spectroscopy.

Accurate real-time determination of each dye in combination dyeing is critical to the control of dyeing process, which plays an important role in upgrading the dyeing techniques of textile. In this work, Raman spectroscopy was applied to dyeing baths containing multiple dye species of varying structures to quantitatively monitor the dyeing process of each individual dye. Quantitative models were successfully established by partial least squares (PLS) for all combinations of the nine commonly used reactive dyes studied. The correlation coefficients were greater than 0.99, the root mean squared errors of calibration (RMSEC) were less than 0.2650 and the root mean squared errors of prediction (RMSEP) were less than 0.1340, even for the three-component mixture of Reactive Red 239 (RR239), Reactive Yellow 176 (RY176) and Reactive Blue 194 (RB194), which are similar in structures. The model was shown to be valid in the presence of added electrolytes (sodium sulfates). Real-time adsorption monitoring based on the model revealed that the dyes interacted with one another and competed for active sites. The adsorption kinetics obtained by Raman analysis shed light on dye compatibility and could be used to guide the design of dyeing recipe and dyeing process for optimum color reproduction. In addition, in situ monitoring by Raman spectroscopy maybe integrated with real-time on line control of dyeing parameters for fully automated production of dyed fabrics.

Characteristics, distribution, source and ecological risk of polycyclic aromatic hydrocarbons (PAHs) in sediments along the Yangtze River Estuary Deepwater Channel.

Characteristics, distribution, source, and ecological risk level of polycyclic aromatic hydrocarbons (PAHs) in sediments along Yangtze River Estuary Deepwater Channel were investigated. Total concentration of fifteen PAHs of study area ranged between 89.52 and 208.02 ng/g (mean value 140.48 ng/g). PAHs ratios and the statistical analysis showed that local fossil fuels high-temperature combustion (vehicular exhaust, anthropogenic combustion and pyrogenic sources) was the main PAHs origin. According to sediment quality guidelines (SQGs) and other criteria, the potential ecological risks of PAHs in sediments along Yangtze River Estuary Deepwater Channel are at low to medium levels, but the presence of dibenzo[a,h]anthracene (DBahAnt) requires more study and evaluation of potential toxicological effects.

Immune-Endocrine System Inspired Hierarchical Coevolutionary Multiobjective Optimization Algorithm for IoT Service.

The intelligent devices in Internet of Things (IoT) not only provide services but also consider how to allocate heterogeneous resources and reduce resource consumption and service time as far as possible. This issue becomes crucial in the case of large-scale IoT environments. In order for the IoT service system to respond to multiple requests simultaneously and provide Pareto optimal decisions, we propose an immune-endocrine system inspired hierarchical coevolutionary multiobjective optimization algorithm (IE-HCMOA) in this paper. In IE-HCMOA, a multiobjective immune algorithm based on global ranking with vaccine is designed to choose superior antibodies. Meanwhile, we adopt clustering in top population to make the operations more directional and purposeful and realize self-adaptive searching. And we use the human forgetting memory mechanism to design two-level memory storage for the choice problem of solutions to achieve promising performance. In order to validate the practicability and effectiveness of IE-HCMOA, we apply it to the field of agricultural IoT service. The simulation results demonstrate that the proposed algorithm can obtain the best Pareto, the strongest exploration ability, and excellent performance than nondominated neighbor immune algorithms and NSGA-II.

An in vitro model of foam cell formation induced by a stretchable microfluidic device.

Although a variety of animal models of atherosclerosis have been developed, these models are time-consuming and costly. Here, we describe an in vitro model to induce foam cell formation in the early stage of atherosclerosis. This model is based on a three-dimension co-culture system in a stretchable microfluidic device. An elastic membrane embedded in the microfluidic device is capable of delivering nonuniform strain to vascular smooth muscle cells, endothelial cells and monocytes adhering thereto, which are intended to mimic the biological environment of blood vessels. Under low-density lipoprotein and stretch treatment, foam cell formation was successfully induced in co-culture with changes in mRNA and protein expression of some related key factors. Subsequently, the model was used to assess the inhibitory effect of atorvastatin on foam cell formation. The results obtained indicate that atorvastatin has a significantly dose-dependent inhibition of foam cell formation, which can be explained by the changes in mRNA and protein expression of the related factors. In principle, the model can be used to study the role of different types of cells in the formation of foam cells, as well as the evaluation of anti-atherosclerotic drugs.

Improved flowing behaviour and gas exchange of stored red blood cells by a compound porous structure.

Storage lesions in red blood cells (RBCs) hinder efficient circulation and tissue oxygenation. The absence of flow mechanics and gas exchange may contribute to this problem. To test if in vitro compensation of flow mechanics and gas exchange helps RBC recovery, three-dimensional polydimethylsiloxane (PDMS) porous structures were fabricated with a sugar mould, simulating lung alveoli. RBC suspensions were passed through the porous structure cyclically, simulating in vivo blood circulation. Acid-base indices, partial gas pressures, ions, glucose and RBC indices were analyzed. An atomic force microscope was used to investigate local mechanical properties of intact RBCs. RBCs suspensions that passed through the porous structures had a higher pH and oxygen partial pressure, and a lower potassium concentration and carbon dioxide partial pressure. Meantime they had better biochemical properties relative to static samples, namely, they exhibited a more homogenous distribution of Young's Modulus. RBCs that passed through a PDMS porous structure were healthier than static ones, giving hints to prevent RBC storage lesions.

Identification of Bioactive Chemical Markers in Zhi zhu xiang Improving Anxiety in Rat by Fingerprint-Efficacy Study.

Zhi zhu xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. The aim of the present work was to identify the bioactive chemical markers in Zhi zhu xiang improving anxiety in rats by a fingerprint-efficacy study. More specifically, the chemical fingerprint of ZZX samples collected from 10 different regions was determined by High Performance Liquid Chromatography (HPLC) and the similarity analyses were calculated based on 10 common characteristic peaks. The anti-anxiety effect of ZZX on empty bottle stimulated rats was examined through the Open Field Test (OFT) and the Elevated Plus Maze Test (EPM). Then we measured the concentration of CRF, ACTH, and CORT in rat's plasma by the enzyme-linked immune sorbent assay (ELISA) kit, while the concentration of monoamine and metabolites (NE, DA, DOPAC, HVA, 5-HT, 5-HIAA) in the rat's cerebral cortex and hippocampus was analysed by HPLC coupled with an Electrochemical Detector. At last, the fingerprint-efficacy study between chemical fingerprint and anti-anxiety effect of ZZX was accomplished by partial least squares regression (PLSR). As a result, we screened out four compounds (hesperidin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C) as the bioactive chemical markers for the anti-anxiety effect of ZZX. The fingerprint-efficacy study we established might provide a feasible way and some elicitation for the identification of the bioactive chemical markers for TCM.