Predicting wheat gluten concentrations in potato starch using GPR and SVM models built by terahertz time-domain spectroscopy.

The purpose of this study was for the first time to explore the feasibility of terahertz (THz) spectral imaging for the detection of gluten contents in food samples. Based on the obtained 80 THz spectrum data, Gaussian process regression (GPR) and support vector machine (SVM) models were established to predict wheat gluten concentrations in 40 potato starch mixture samples. The prediction performances of GPR and SVM obtained were R2 = 0.859 and RMSE = 0.070, and R2 = 0.715 and RMSE = 0.101 in the gluten concentration range of 1.3%-100%, respectively, showing that the linear SVM algorithm had better prediction performance. The results indicated that THz spectral imaging combined with GPR could be used to predict the gluten content in food samples. It is thus hoped that this research should provide a novel technique for gluten content detection to ensure gluten-free food samples.

Chitosan inhibits vascular intimal hyperplasia via LINC01615/MIR-185-5p/PIK3R2 signaling pathway.

The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are the main pathological processes which are involved in the formation of new intima. In our previous study, we found that chitosan can inhibit the formation of new intima in the arteriovenous fistulas of uremic patients, and the expression of LINC01615 was significantly increased in patients after treatment with chitosan. Therefore, this study aims to further explore the effect of chitosan on the intimal hyperplasia and elucidate the potential molecular mechanism. In vitro, we found that in chitosan-treated VSMC, the levels of Il-1ß, IL-6 and TNF-α decreased, and the intimal hyperplasia was inhibited along with significantly downregulated PIK3R2 and upregualted PI3K, AKT and p-AKT. Meanwhile, we observed the phenotypic transformation of hVSMCs after LINC01615 was upregulated. In addition, inflammatory factors showed the same changes in the process of up-regulating LINC01615. Moreover, only in the LINC01615 overexpression and miR-185-5p mimic experimental group, the inhibition of intimal hyperplasia was the most obvious. The interaction between LINC01615 and miR-185-5p, miR-185-5p and PIK3R2 was further confirmed by the dual luciferase assay. These results suggest that chitosan has a potential preventive effect on neointimal hyperplasia and related vascular remodeling.

Facile synthesis of multicolor emitting sulfur quantum dots and their applications in light blocking field, anti-counterfeiting and sensing.

Sulfur quantum dots (SQDs) have aroused widespread interest from researchers in a wide range of fields due to their excellent photoluminescent properties. Ethylenediamine, diaminopropane and butanediamine were used as precursor amine raw materials to interact with sublimated sulfur to synthesize SQDs with blue, cyan and green fluorescence emission, respectively. Multicolour emitting SQDs were first prepared via sulfur-amine interactions. Further characterization and calculations showed that the precursor amine substances could alter growth size and band gap energy of SQDs to allow for a wider absorption and fluorescence transfer to long wavelength emission region, resulting in tunable fluorescence emission. In terms of application, the excellent down-conversion properties of SQDs were utilized to obtain highly transparent and flexible photoblocking films by blending SQDs with polyvinyl alcohol matrixes, achieving a blocking of light in UV region of up to 99.69 %. In addition, we constructed an encoded storage microarray based on standard 8-bit ASCII character binary codes using BSQDs and GSQDs to store and encrypt important information. Finally, GSQDs-based fluorescent sensors were designed to achieve fluorescent trace detection of o-nitrophenols with limits of detection as low as 2.54 µM. The multicolor emitting SQDs prepared in this work have great potential for applications in analytical detection, optical anti-counterfeiting and light blocking.

Bisphenol and analogues in indoor dust from E-waste recycling sites, neighboring residential homes, and urban residential homes: Implications for human exposure.

The compound 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP) has recently emerged as a novel alternative to bisphenol A (BPA) and has been found in various paper products. However, there is limited information available regarding the identification of BPSIP as a novel contaminant in the e-waste dismantling area. In our research, we conducted a comprehensive analysis of 16 bisphenol analogues (BPs), including BPSIP, within indoor dust samples obtained from a representative e-waste recycling facility, neighboring rural communities, and control urban communities. Out of the 16 target BPs, ten were found in both e-waste and local household dust, while only six BPs were identified in the control urban household dust. Bisphenol A (BPA) remained the predominant compound, followed by bisphenol F (BPF), bisphenol S (BPS), BPSIP and bisphenol AF (BPAF). The total concentrations of BPs in e-waste dust were notably higher compared to both local and urban household dust (p < 0.01), with BPA and BPF, in particular, exhibiting significantly elevated levels. Importantly, BPSIP was first identified in e-waste dust, and its concentration significantly exceeded that of the commonly used BPA alternative, BPAF, which justifiably merits increasing concern. Correlation analysis indicated that BPs were commonly used in the production of electronic products, and e-waste dismantling activities contributed significantly to their widespread emission. The daily intakes of BP through dust ingestion for these three population groups exceeded the recently established tolerable daily intake for BPA, especially among e-waste dismantling workers. This represents the first report indicating that e-waste recycling is causing substantial emissions of multiple bisphenol analogues, including a novel contaminant.

Biomonitoring of glyphosate and aminomethylphosphonic acid: Current insights and future perspectives.

Glyphosate is one of the most widely used herbicides globally, raising concerns about its potential impact on human health. Biomonitoring studies play a crucial role in assessing human exposure to glyphosate and providing valuable insights into its distribution and metabolism in the body. This review aims to summarize the current trends and future perspectives in biomonitoring of glyphosate and its major degradation product of aminomethylphosphonic acid (AMPA). A comprehensive literature search was conducted, focusing on studies published between January 2000 and December 2022. The findings demonstrated that glyphosate and AMPA have been reported in different human specimens with urine as the dominance. Sample pretreatment techniques of solid-phase and liquid-liquid extractions coupled with liquid/gas chromatography-tandem mass spectrometry have achieved matrix elimination and accurate analysis. We also examined and compared the exposure characteristics of these compounds among different regions and various populations, with significantly higher levels of glyphosate and AMPA observed in Asian populations and among occupational groups. The median urinary concentration of glyphosate in children was 0.54 ng/mL, which was relatively higher than those in women (0.28 ng/mL) and adults (0.12 ng/mL). It is worth noting that children may exhibit increased susceptibility to glyphosate exposure or have different exposure patterns compared to women and adults. A number of important perspectives were proposed in order to further facilitate the understanding of health effects of glyphosate and AMPA, which include, but are not limited to, method standardization, combined exposure assessment, attention for vulnerable populations, long-term exposure effects and risk communication and public awareness.

Hematoporphyrin derivative photodynamic therapy induces apoptosis and suppresses the migration of human esophageal squamous cell carcinoma cells by regulating the PI3K/AKT/mTOR signaling pathway.

Esophageal cancer is one of the most common cancer types in humans worldwide. Photodynamic therapy (PDT) is a promising therapeutic strategy for the treatment of cancer. However, its underlying mechanism needs to be studied thoroughly. The present study focused on the antitumor effect and underlying mechanism of the use of hematoporphyrin derivative (HpD)-PDT against human esophageal squamous cell carcinoma cells via regulation of the PI3K/AKT/mTOR signaling pathway. A Cell Counting Kit-8 assay was used to measure cell viability. Migration was evaluated using a wound healing assay. An annexin V-FITC/PI kit was used to determine cell apoptosis rates. Protein expression levels were analyzed via western blotting. Reverse transcription-quantitative PCR was used to detect gene expression levels. A 2',7'-dichlorodihydrofluorescein diacetate kit was chosen to evaluate intracellular reactive oxygen species levels via flow cytometry. Cell viability and migration were decreased in KYSE-150 cells after HpD-PDT treatment. Cellular apoptosis was induced after HpD-PDT treatment, and the same trend was observed for autophagy. Furthermore, the PI3K/AKT/mTOR signaling pathway was inhibited. The viability and migration of KYSE-150 cells were significantly inhibited, and apoptosis was induced more effectively following treatment with a combination of HpD-PDT and the PI3K inhibitor, a final concentration of 20 µM LY294002. In conclusion, HpD-PDT could suppress esophageal cancer cell viability, induce apoptosis and inhibit migration by downregulating the PI3K/AKT/mTOR signaling pathway. Combination of HpD-PDT with PI3K inhibitor (LY294002) could enhance the therapeutic efficacy compared with that demonstrated by HpD-PDT alone. Further studies on combination therapy are required to achieve improved clinical outcomes.

Near-infrared Chemiluminescence Imaging of Chemotherapy-induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) has a high prevalence but is poorly managed for cancer patients due to the lack of reliable and sensitive diagnostic techniques. Molecular optical imaging can provide a noninvasive way for real-time monitoring of CIPN. However, this has not been reported, likely due to the absence of optical probes capable of imaging deep into the spinal canal and possessing sufficient sensitivity for minimal dosage through local injection into the dorsal root ganglia. Herein, we synthesize a near-infrared (NIR) chemiluminophore (MPBD) with a chemiluminescence quantum yield higher than other reported probes and develop it into a NIR activatable chemiluminescent probe (CalCL) for in vivo imaging of CIPN. CalCL is constructed by caging MPBD with calpain-cleavable peptide moiety while conjugating polyethylene glycol chain to endow water solubility. Due to the deep-tissue penetration of chemiluminescence and specific turn-on response of CalCL towards calpain (a hallmark of CIPN), it allows for sensitive detection of paclitaxel-mediated CIPN in living mice, which is unattainable by fluorescence imaging. This study thus not only develops a highly efficient chemiluminescent probe but also presents the first optical imaging approach toward high-throughput screening of neurotoxic drugs. This article is protected by copyright. All rights reserved.

Short-term and long-term efficacy of sublingual immunotherapy in different courses for house dust mite-induced allergic rhinitis.

PURPOSE: Sublingual immunotherapy (SLIT) has been proven to be an effective and safe treatment for patients with house dust mite (HDM)-induced allergic rhinitis (AR) to achieve short-term and long-term efficacy. This study aimed to investigate the relationship between SLIT duration and long-term efficacy. MATERIALS AND METHODS: This study involved 134 patients who underwent SLIT between 2019 and 2021 (in the 2-year group), between 2018 and 2021(in the 3-year group), or between 2017 and 2021 (in the 4-year group). The total nasal symptoms score (TNSS), total medication score (TMS), visual analogue scale (VAS), the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) and adverse events (AEs) were assessed at baseline, after treatment (2021) and one year after the treatment completion (2022). The correlation between MiniRQLQ and other indicators was also analyzed. RESULTS: After SLIT, patients in all three groups showed significant improvements in TNSS, TMS, VAS and MiniRQLQ scores (all p < 0.001). These improvements were sustained even one year after SLIT. Patients who received 3-4 years of SLIT showed significant improvement compared with those who received 2 years of SLIT in all clinical outcomes (all p < 0.01). The analysis showed positive correlations between the MiniRQLQ and TNSS, TMS, and VAS (all p < 0.001). No significant difference was observed in the AE rate in all three groups (p > 0.05). CONCLUSION: Different duration of HDM SLIT could generate various short-term and long-term clinical efficacy. The MiniRQLQ could be applied to evaluate SLIT efficacy in clinical practice.

Potato virus Y viral protein 6K1 inhibits the interaction between defense proteins during virus infection.

14-3-3 proteins play vital roles in plant defense against various pathogen invasions. To date, how 14-3-3 affects virus infections in plants remains largely unclear. In this study, we found that Nicotiana benthamiana 14-3-3 h interacts with TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (TCTP), a susceptibility factor of potato virus Y (PVY). Silencing of Nb14-3-3 h facilitates PVY accumulation, whereas over-expression of Nb14-3-3 h inhibits PVY replication. The antiviral activities of three Nb14-3-3 h dimerization defective mutants are significantly decreased, indicating that dimerization of Nb14-3-3 h is indispensable for restricting PVY infection. Our results also showed that the mutant Nb14-3-3hE16A, which is capable of dimerizing but not interacting with NbTCTP, has reduced anti-PVY activity; the mutant NbTCTPI65A, which is unable to interact with Nb14-3-3 h, facilitates PVY replication compared to the wild-type NbTCTP, indicating that dimeric Nb14-3-3 h restricts PVY infection by interacting with NbTCTP and preventing its pro-viral function. As a counter-defense, PVY 6K1 interferes with the interaction between Nb14-3-3 h and NbTCTP by competitively binding to Nb14-3-3 h and rescues NbTCTP to promote PVY infection. Our results provide insights into the arms race between plants and potyviruses.

A combined screening study for evaluating the potential of exhaled acetone, isoprene, and nitric oxide as biomarkers of lung cancer.

Background: the early lung cancer (LC) screening strategy significantly reduces LC mortality. According to previous studies, lung cancer can be effectively diagnosed by analyzing the concentration of volatile organic compounds (VOCs) in human exhaled breath and establishing a diagnosis model based on the different VOCs. This method, called breath analysis, has the advantage of being rapid and non-invasive. To develop a non-invasive, portable breath detection instrument based on cavity ring-down spectroscopy (CRDS), we explored the feasibility of establishing a model with acetone, isoprene, and nitric oxide (NO) exhaled through human breath, which can be detected on the CRDS instrument. Methods: a total of 511 participants were recruited from the Cancer Institute and Hospital, Tianjin Medical University as the discovery set and randomly split (2 : 1) into training set and internal validation set with stratification. For external validation, 51 participants were recruited from the General Hospital, Tianjin Medical University. Acetone and isoprene from exhaled breath were detected by proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS), and NO was measured using CRDS. The model was constructed using the ensemble learning method that set eXtreme gradient boosting and logistic regression as the basis model and logistic regression as the senior model. The model was evaluated based on accuracy, sensitivity, and specificity. Results: the model achieved an accuracy of 78.8%, sensitivity of 81.0%, specificity of 70.0%, and area under the receiver operating curve (ROC, AUC) of 0.8341 (95% CI from 0.8055 to 0.8852) in the internal validation set. Furthermore, it attained an accuracy of 66.7%, sensitivity of 68.2%, specificity of 65.5%, and AUC of 0.6834 (95% CI from 0.5259 to 0.7956) in the external validation set. Conclusion: the model, established with acetone, isoprene, and NO as predictors, possesses the ability to identify LC patients from healthy control (HC) participants. The CRDS instrument, which simultaneously detects acetone, isoprene, and NO, is expected to be a non-invasive, rapid, portable, and accurate device for early screening of LC.

A Novel Angle Segmentation Method for Magnetic Encoders Based on Filtering Window Adaptive Adjustment Using Improved Particle Swarm Optimization.

In this paper we outline newly-developed control algorithms, designed to achieve high-precision feedback for a motor control system using a magnetic encoder. The magnetic encoder, combing single-pole and multi-pole magnetic steels, was adopted to extend the resolution of the magnetic encoder. First, with a view to settling the issue of the jump points of the multi-pole angle value at the convergence of two adjacent magnetic poles, the angle segmentation method, which uses the window filter discrimination method, is employed to determine the actual angle value. The appropriate filter window width is selected via the improved particle swarm optimization (IPSO) algorithm, and an expanded resolution is achieved. Second, a compensation table is completed via a linear compensation algorithm based on virtual cutting to enhance the accuracy of the combined magnetic encoder. On this basis, a linear difference algorithm is used to achieve deviation correction of the angle. Finally, the jump points can be restrained effectively via the angle segmentation method. The resolution reaches 0.05°, and the accuracy is 0.045°.

Study on the movement mechanism of rice stem under the action of canopy-opening device based on explicit dynamics simulation.

The dense canopy of rice causes attenuation of droplet dispersion during pesticide application. The canopy-opening device can increase droplet deposition in the middle and lower canopy of rice by causing disturbance to the rice canopy. However, the conditions for use of the canopy-opening device are difficult to determine. Rice morphological structure parameters and material parameters were measured to study the movement mechanism of the rice stems under the action of the canopy-opening device, and the canopy-opening process was then simulated using the explicit dynamic method. The simulation scene of the rice canopy-opening process considered the combination of three different heights and three different driving velocities of the canopy-opening device. The movement mechanism of the rice stems under the operation of the canopy-opening device was investigated, and the entire movement process was separated into two stages: contact and oscillation. The simulation results and high-speed photography experimental results show a strong correlation, with a correlation coefficient of 0.733. The simulation results indicate that when the canopy-opening device is closer to the ground and the driving velocity is higher, the disturbance to the rice stem during the contact stage is stronger. However, for the oscillation stage, there exists a critical value for both the height and driving velocity of the canopy-opening device. During the oscillation stage, there is a critical value for both the height and driving velocity of the canopy-opening device. The numerical-based explicit dynamics approach was employed in this work to investigate the rice canopy motion mechanism, and this study has a definite reference value for the investigation of complicated motion mechanisms in the field crop production process.

Target ssDNA activates the NADase activity of prokaryotic SPARTA immune system.

Argonaute proteins (Agos), which use small RNAs or DNAs as guides to recognize complementary nucleic acid targets, mediate RNA silencing in eukaryotes. In prokaryotes, Agos are involved in immunity: the short prokaryotic Ago/TIR-APAZ (SPARTA) immune system triggers cell death by degrading NAD+ in response to invading plasmids, but its molecular mechanisms remain unknown. Here we used cryo-electron microscopy to determine the structures of inactive monomeric and active tetrameric Crenotalea thermophila SPARTA complexes, revealing mechanisms underlying SPARTA assembly, RNA-guided recognition of target single-stranded DNA (ssDNA) and subsequent SPARTA tetramerization, as well as tetramerization-dependent NADase activation. The small RNA guides Ago to recognize its ssDNA target, inducing SPARTA tetramerization via both Ago- and TIR-mediated interactions and resulting in a two-stranded, parallel, head-to-tail TIR rearrangement primed for NAD+ hydrolysis. Our findings thus identify the molecular basis for target ssDNA-mediated SPARTA activation, which will facilitate the development of SPARTA-based biotechnological tools.

CircMIRLET7BHG, upregulated in an m6A-dependent manner, induces the nasal epithelial barrier dysfunction in allergic rhinitis pathogenesis.

OBJECTIVE: Allergic rhinitis (AR) remains a frequent aspiratory allergic inflammatory disorder with a high incidence. Circular RNAs (circRNAs) have been revealed to participate in the pathogenesis of AR. This study investigated the biological function of circMIRLET7BHG (hsa_circ_0008668) in AR progression. METHODS: Ovalbumin (OVA)-exposed human nasal epithelial cell line (HNEpC) and mice were adopted as the in vitro and in vivo models of AR. Immunofluorescence staining was used to determine epithelial tight junction protein expression. Target molecule levels were assessed by RT-qPCR and Western blotting. Localization of circMIRLET7BHG and IGF2BP1 was observed by RNA-FISH and immunofluorescence. Epithelial barrier damage was determined by transepithelial electrical resistance and fluorescein isothiocyanate-dextran (FD4) permeability. Serum concentrations of IgE, sIgE, IFN-γ, IL-4, and IL-5 were detected by ELISA. Apoptosis, pathological changes, and eosinophil infiltration in nasal mucosa tissues were evaluated by TUNEL, H&E, and Sirius red staining, respectively. Molecular mechanism was analyzed by RNA pull-down, RIP, and MeRIP assays. RESULTS: An increased expression of circMIRLET7BHG was found in AR patients and experimental models. Down-regulation of circMIRLET7BHG attenuated OVA-induced allergic symptoms via relieving epithelial thicknesses, eosinophil infiltration, apoptosis, and inflammatory response in mice. Subsequently, circMIRLET7BHG deficiency prevented OVA-induced epithelial barrier dysfunction by reducing epithelial permeability, and inhibiting tight junction proteins. Mechanistically, methyltransferase-like 3 (METTL3) enhanced circMIRLET7BHG expression via m6A methylation, which enhanced ADAM10 mRNA stability via interaction with IGF2BP1. CONCLUSION: METTL3-mediated m6A modification increased circMIRLET7BHG expression that consequently raised ADAM10 mRNA stability via interplay with IGF2BP1, thereby promoting AR by inducing epithelial barrier dysfunction.

The role of vitamin D through SphK1/S1P in the regulation of MS progression.

Sphingosine-1-phosphate (S1P) is biologically active lipid, leading to neuroinflammation and macrophage invasion in central nervous system, plays an important role in the development of multiple sclerosis (MS) model in experimental allergic encephalomyelitis (EAE) rats. Vitamin D is observed to be a key factor in regulating cell S1P levels. We detected vitamin D can alleviate the symptoms of EAE rats, but the exact mechanism is unclear. In PC12 cells, vitamin D can reverse S1P-induced cell death, but the signaling pathway unclear. This study was aimed to investigate S1P regulation mechanism or signaling pathway mediated by vitamin D in EAE and PC12 model. In our experiments, S1P and Sphingosine kinase type 1 (SphK1) mRNA and protein expression in EAE rats group, control group, vitamin D feeding group were detected by HPLC, ELISA, RT-PCR and western blot. PC12 cell death was detected by Propidium (PI) staining. VDR plasmid overexpression and RNA interference, immunofluorescence, real-time cell analysis, protein immunoblotting was used to detect SphK1 transcriptional regulation, cell-substrate attachment quality, the signaling pathway of cell apoptosis and inflammation related gene expression (Bax/Bcl-2, Casepase-3, Il-6, TGF-ß, TNF-α). Our study showed vitamin D can reverse the elevation of S1P level in EAE rats, reduce the severity and shorten the course of EAE. 1,25-(OH) 2D3 coupled with vitamin D receptor (VDR) inhibited SphK1 transcription. 1,25-(OH)2D3 significantly reduced PC12 cell death rate induced by S1P, in addition improved the cell substrate attachment quality. 1,25-(OH) 2D3 can block S1P-induced p-ERK activation and PI3K /Akt signaling pathway reduced Il-6, TGF-ß, TNF-α cytokine release and Bax/Bcl-2, Casepase-3 apoptosis protein expression. On the other hand, immunofluorescence staining showed 1,25-(OH) 2D3 can increase the expression of neuronal perinuclear protein MAP2 in PC12 cells probably protect nerve cells further. In summary, the ameliorative effect of vitamin D was derived from its ability to reduce S1P levels, provides an idea for vitamin D as a combination therapy for disease.

DeepPatent2: A Large-Scale Benchmarking Corpus for Technical Drawing Understanding.

Recent advances in computer vision (CV) and natural language processing have been driven by exploiting big data on practical applications. However, these research fields are still limited by the sheer volume, versatility, and diversity of the available datasets. CV tasks, such as image captioning, which has primarily been carried out on natural images, still struggle to produce accurate and meaningful captions on sketched images often included in scientific and technical documents. The advancement of other tasks such as 3D reconstruction from 2D images requires larger datasets with multiple viewpoints. We introduce DeepPatent2, a large-scale dataset, providing more than 2.7 million technical drawings with 132,890 object names and 22,394 viewpoints extracted from 14 years of US design patent documents. We demonstrate the usefulness of DeepPatent2 with conceptual captioning. We further provide the potential usefulness of our dataset to facilitate other research areas such as 3D image reconstruction and image retrieval.

A study on the correlation between MTHFR and folic acid combined with trace elements for the prevention of fetal malformations in the first trimester of pregnancy.

This study aims to elucidate and examine the intricate interrelation between 5,10-methylenetetrahydrofolate reductase (MTHFR), combined folic acid (FA), and trace element supplementation as a preventive strategy against fetal malformations during the inaugural trimester of pregnancy. Eighty pregnant women selected from our hospital's early obstetrics department from May 2021 to August 2021. Pregnant women are divided into the MTHFR combined group, FA, and trace element group. Comparing the basic data of patients, analyzing adverse reactions in pregnant women, and total birth risk situation, detecting MTHFR gene polymorphisms, and analyzing the correlation between MTHFR and FA in the prevention of fetal malformations in early pregnancy. Compared with the north, the southern region is more prone to FA deficiency. MTHFR degree of the MTHFR combined group was positively correlated with fetal malformations. The deformity rate was negatively correlated with FA and trace elements. Pregnant women in the first trimester may have fetal malformations, and the malformation rate is negatively correlated with FA and positively correlated with MTHFR level. Importantly, the inverse relationship between FA supplementation and malformation incidence underscores its significance as a preventive measure.

Cherry leaf decoction inhibits NMDAR expression and thereby ameliorates CUMS- induced depression-like behaviors through downregulation of α2δ-1.

Depression is a complex and prevalent mental illness. Cherry leaf is a traditional Chinese herbal medicine, which has confirmed to exert a certain antidepressant effect, but its potential neural regulation mechanism is not clear. This paper aims to investigate the improved action of cherry leaf decoction (CLD) on chronic unpredictable mild stress (CUMS) rats and its potential neural regulation mechanism by verifying the role and function of NMDAR regulatory target α2δ-1 in depression due to CUMS. Male SD rats were subjected to random stressors persisting for 5 weeks to establish the CUMS depression rat model. CLD could effectively alleviate depression-like behaviors of CUMS rats in behavioral tests including sucrose preference test, forced swimming test, tail suspension test and open field test. After the administration of the CLD, the expression of corticotropic-releasing hormone (CRH) in the hypothalamus was inhibited. Moreover, the levels of CRH, adrenal cortical hormone (ACTH) and corticosterone (CORT) in serum also decreased significantly. CUMS upregulated the expressions of α2δ-1, N-methyl-d-aspartate receptor 1 (NR1), NR2A and NR2B, and enhanced the binding ability to of α2δ-1 and NR1, which were reversed by CLD. The results demonstrated that CLD could ameliorate depression-like behaviors due to CUMS, which was related to the fact that CLD down-regulated α2δ-1 level and interfered with α2δ-1 binding to NR1, thereby reducing NMDAR expression and ultimately inhibiting HPA axis activity.

New Monoterpenoid Indole Hybrids from Gelsemium elegans with Anti-Inflammatory and Osteoclast Inhibitory Activities.

Gelsegansymines A (1) and B (2), two new indole alkaloids along with six known analogues (3-8) were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques. Structurally, compounds 1 and 2 possessed the rare cage-like gelsedine skeleton hybrid with bicyclic monoterpenoid. The anti-inflammatory activities of isolated compounds (1-3) were tested on LPS induced RAW264.7 cells. Under the treated concentration without toxicity for cells, the cytokines levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were evaluated by Griess method and enzyme-linked immunosorbent assay (ELISA). The results showed that compounds 1-3 exhibited anti-inflammatory activities with dose-dependent manner range from 12.5 to 50 µmol/L. Furthermore, the inhibitory activities of compounds 1 and 2 on receptor activator of NF-κB ligand (RANKL) induced osteoclast formation were tested in vitro. Compounds 1 and 2 at 5 µmol/L exhibited the significant inhibitory effect on the osteoclastogenesis induced by RANKL. This work reported the anti-inflammatory and osteoclast inhibitory activities of new monoterpenoid indole hybrids, which may inspire the further light on the related traditional application research of G. elegans.