OBJECTIVE To investigate the ameliorative effect and mechanism of short-acting exenatide on diabetic cognitive dysfunction. METHODS Spontaneously diabetic db / db mice were randomly divided into model group （normal saline） and exenatide group （50 μg/kg）， with db / m mice as the normal control group （normal saline）， with 8 mice in each group. Mice in each group were subcutaneously injected with corresponding drugs or normal saline twice daily for 8 consecutive weeks. Body weight and fasting blood glucose were measured at a fixed time every week. Cognitive function was evaluated by Morris water maze test. The levels of oxidative st ress indicators [malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH） ] ， cyclic adenosine monophosphate （cAMP） and protein kinase A （PKA） were detected in hippocampus tissue of mice. The hippocampal neuronal HT22 cells of mice were divided into control group （25 mmol/L glucose）， high glucose group （125 mmol/L glucose）， high glucose+exenatide group （125 mmol/L glucose+20 nmol/L exenatide）， high glucose+exenatide+H89 （PKA inhibitor） group （125 mmol/L glucose+20 nmol/L exenatide+10 μmol/L H89）， and high glucose+H89 group （125 mmol/L glucose+10 μmol/L H89）. After 48 h of intervention with corresponding solutions/culture medium， the levels of oxidative stress indicators， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and the phosphorylation level of dynamin-related protein 1 （Drp1） were measured. RESULTS Animal experiments showed that compared with the normal control group， the model group exhibited significantly increased body weight， fasting blood glucose and MDA level in the hippocampus （ P ＜0.05）， as well as significantly prolonged escape latency （ P ＜0.05）； swimming speed significantly slowed down， the time spent in the target quadrant， the number of platform crossings， and the levels of SOD， GSH， cAMP and PKA in the hippocampus were significantly decreased （ P ＜0.05）. Compared with model group， all the above indicators （except for swimming speed） in the exenatide group were significantly reversed （ P ＜0.05）. Cell experiments showed that compared with high glucose group， the high glucose+exenatide group had significantly decreased MDA level （ P ＜0.05）， and significantly increased levels of SOD， GSH， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and phosphorylation level of Drp1 （ P ＜0.05）. Compared with high glucose+exenatide group， the above indicators in the high glucose+exenatide+H89 group were significantly reversed （ P ＜0.05）. CONCLUSIONS Short-acting exenatide can activate the cAMP/PKA pathway， promote Drp1 phosphorylation， and increase the activities of mitochondrial respiratory enzymes， thereby maintaining mitochondrial stability， reducing oxidative stress injury， and ultimately improving diabetic cognitive dysfunction.

BACKGROUND:Post and core restoration is a common choice for tooth defects,but the repair effects of various post and core materials are different. OBJECTIVE:To evaluate the stress distribution at the post and core,tooth root,and bonding agent site of post and core models made of different elastic modulus post and core materials using finite element method. METHODS:A three-dimensional root canal treated maxillary central incisor model was built using three-dimensional modeling software,which was restored with a full ceramic crown.The post and core materials in the restoration used nanoceramic resin(elastic modulus=12.8 GPa),composite resin(elastic modulus=16 GPa),hybrid ceramic(elastic modulus=34.7 GPa),glass ceramic(elastic modulus=95 GPa),titanium alloy(elastic modulus=112 GPa),and zirconia(elastic modulus=209.3 GPa).The model was fixed in cortical bone.A 100 N concentrated force of 45° from the long axis of the tooth was applied to 1/3 of the crown and tongue side of the central incisor.The stress distribution of the post and core,dentin,and tooth-root bonding agent in the model was repaired by the maximum principal stress criterion. RESULTS AND CONCLUSION:(1)When the post and core materials with higher elastic modulus was used,the post-core stress in the repair model was more concentrated.When the elastic modulus of the post and core materials(nanoceramic resin and composite resin)was close to dentin,the stress distribution of the post and core was more uniform.The stress distribution of dentin in all restoration models was similar regardless of post and core materials.When the post and core with higher elastic modulus was used,more stress concentration was shown at the post and root bonding agent in the repair model.(2)The maximum stress values at the post and core,tooth root,and the bonding agent site of post and tooth root in the nanoceramic resin model were 31.00,33.21,and 0.51 MPa,respectively.The maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root in the composite resin model were 36.84,33.14,and 0.59 MPa,respectively.In the mixed ceramic model,the maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root were 64.05,32.83,and 1.00 MPa,respectively.In the glass ceramic model,the maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root were 112.30,32.69,and 1.73 MPa,respectively.In the titanium alloy model,the maximum stress values of the post and core,tooth root,and the bonding agent between the post and tooth root were 120.00,32.17,and 1.86 MPa,respectively.In the zirconia model,the maximum stress values of the post and core,tooth root,and the bonding agent between the post and tooth root were 148.80,31.85,and 2.28 MPa,respectively.(3)The higher the elastic modulus of the post and core material,the higher the maximum stress at the post and core during restoration.The elastic modulus of the post and core material had no significant effect on the maximum stress of the dental bonding agent and dentin.

A new method was developed for simultaneous and efficient determination of linear perfluorooctanoic acid(n-PFOA)and linear perfluorooctane sulfonate(n-PFOS),and their typical branched isomers in seawater by online solid phase extraction-liquid chromatography-tandem mass spectrometry(Online SPE-LC-MS/MS).Only centrifugation of the seawater sample was required to remove the particulate matter,and then the seawater sample was directly injected and analyzed by online SPE-LC-MS/MS.An Eclipse Plus-C18 guard column was selected as SPE column for online enrichment of linear and branched isomers,and a F5 PFP column(150 mm×2.1 mm,2.7 μm)was used as the analytical column.Under the optimized experimental conditions,the separation and detection of all PFOA and PFOS linear and branched isomers could be completed within 20 min.The spiked recoveries of various target compounds ranged from 82.9%to 107.7%with detection limits and limits of quantification of 0.10-1.05 ng/L and 0.30-2.11 ng/L,respectively.The method was characterized by good precision(RSD≤9.10%)and linearity(R2≥0.990).Subsequently,linear and branched isomers of PFOA and PFOS in surface and bottom seawater samples collected from the Laizhou Bay of China were determined.The results showed that the detection rate of all the four branched PFOA isomers were 100%,with the highest average concentration of 25.85 ng/L found for 6m-PFOA,which accounted for 11.79%of the∑PFOA.For the five branched isomers of PFOS,the highest detection rate of 90.84%was found for 5m-PFOS.The highest average concentration of 0.64 ng/L was observed for 3m-PFOS,accounting for 19.88%of ∑PFOS.The proposed method provided an effective detection tool for qualitative and quantitative detection of PFOA and PFOS isomers in the marine aquatic environment.

An efficient analytical method was developed for simultaneous detection of alkylamines and alkylamides in food packaging plastics using liquid chromatography-high resolution mass spectrometry(LC-HRMS).Based on the physicochemical properties of alkylamines and alkylamides,as well as the complexity of plastic samples,sample pretreatment and chromatographic-mass spectrometric parameters were optimized.The samples were extracted by vortex-ultrasonic extraction with a methanol-acetonitrile mixture for 15 min,followed by nitrogen evaporation to concentrate the extract,reconstitution,and analysis.The chromatographic mobile phase consisted of 0.1%formic acid aqueous solution and acetonitrile,and a gradient elution was used.The electrospray ionization(ESI)source was operated in positive ion mode,and mass spectrometry data were collected in full scan and data-dependent acquisition modes.Quantification was performed using an isotope-labeled internal standard method.The results showed that within the quantification range of 1-1000 ng/mL,the calibration curves exhibited good linearity(R2>0.99).Some compounds interfered with the validation experiments at higher concentrations,so only 10 kinds of target analytes were validated.Using a mixed food packaging plastic matrix,the recoveries at spiking levels of 40,400,and 4000 ng/g were mostly between 66.0%and 117.1%,with relative standard deviations ranging from 0.6%to 10.6%.The method was applied to detect 14 food packaging plastic samples,and the results showed that the concentrations of alkylamines and alkylamides ranged from not detected to 8924 ng/g.This method offered high sensitivity and accuracy,and was suitable for the screening and quantitative determination of alkylamines and alkylamides in plastics.

A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.

Aerosol-assisted plasma amplification laser-induced breakdown spectroscopy(LIBS)was employed for phosphorus detection in water.To address the multivariate coupling effects in LIBS and nebulization sampling system,an orthogonal experiment was employed to systematically optimize the key experimental parameters.Using the orthogonal experimental design,the parametric effects of laser energy(output voltage),signal acquisition delay,liquid velocity,and gas velocity on the signal to background ratio(SBR)of P I 213.618 nm were evaluated,and the optimal conditions were achieved,including laser energy of 86 mJ,delay time of 3 μs,gas velocity of 1.05 mL/min,and liquid velocity of 60 μL/min,which were in agreement with the control-variable optimization results.Moreover,the SBR response trends at P I 213.618 nm with all experimental parameters was strong in consistency with control-variable optimization results,which demonstrated the validity of the orthogonal array experimental design.This study established an efficient and accurate parameter optimization methodology for complex LIBS systems,significantly advancing the application of LIBS in environmental monitoring.

Objective To investigate the effect of Qingchi Powder(composed of calamina,Halloysitum Rubrum,Phellodendri Chinensis Cortex,Sophorae Flavescentis Radix,Catechu,Indigo Naturalis,Rhizoma Bletillae,and Notoginseng Radix et Rhizoma powder)retention enema on intestinal flora and Toll-like receptor 4(TLR4)/NOD-like receptor thermoprotein domain-related protein 3(NLRP3)signaling pathway in peripheral blood mononuclear cell(PBMC)of children with ulcerative colitis(UC).Methods A total of 100 children with UC were randomly divided into control group and study group,with 50 cases in each group.The control group was treated with oral administration of Mesalazin Enteric-Coated Tablets,and the study group was treated with Qingchi Powder retention enema on the basis of treatment for the control group.The treatment for the two groups lasted for 8 consecutive weeks.Before and after treatment,the distribution of intestinal flora and the relative mRNA expression levels of TLR4 and NLRP3 in PBMC,serum contents of TLR4 and NLRP3 protein,and serum levels of inflammatory factors such as tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)and interleukin 6(IL-6)in the two groups were observed.After treatment,the clinical efficacy of the two groups was evaluated,and Spearman test was used to analyze the correlation of total effective rate with the relative mRNA expression levels of TLR4 and NLRP3 in PBMC and serum contents of TLR4 and NLRP3 protein.Results(1)After 8 weeks of treatment,the total effective rate of the study group was 94.00%(47/50),and that of the control group was 70.00%(35/50).The intergroup comparison(tested by chi-square test)showed that the efficacy of the study group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the number of Enterococcus and Enterobacteriaceae in the two groups was significantly lowered(P＜0.05),and the number of Bifidobacterium and Lactobacillus was significantly increased compared with that before treatment(P＜0.05).After treatment,the number of Enterococcus and Enterobacteriaceae in the study group was significantly lower(P＜0.05)and the number of Bifidobacterium and Lactobacillus was significantly higher than that in the control group(P＜0.05).(3)After treatment,the mRNA relative expression levels of TLR4 and NLRP3 in PBMC of the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels in the study group were significantly lower than those in the control group(P＜0.05).(4)After treatment,the serum TLR4 and NLRP3 protein levels in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels in the study group were significantly lower than those in the control group(P＜0.05).(5)After treatment,the levels of serum inflammatory factors of TNF-α,IL-1β and IL-6 in the two groups significantly decreased compared with those before treatment(P＜0.05),and the levels in the study group were significantly lower than those in the control group(P＜0.05).(6)Spearman correlation analysis showed that the mRNA relative expression levels of TLR4 and NLRP3 in PBMC and serum TLR4 and NLRP3 protein levels in children with UC were significantly negatively correlated with the total effective rate of curative effect(P＜0.001).Conclusion Qingchi Powder retention enema can down-regulate the expression levles of key signaling molecules of TLR4/NLRP3 pathway in PBMC of children with UC,regulate the intestinal flora of children,and improve the inflammatory response.It has significant curative effect and is worthy of expanding its application in clinic.

Programmed cell death (PCD) is characterized as a cell death pathway governed by specific gene-encoding requirements, plays crucial roles in the homeostasis and innate immunity of organisms, and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases. Z-DNA-binding protein 1 (ZBP1) functions as a cytosolic nucleic acid sensor, utilizing its unique Zα domains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif (RHIM) domains to sense or bind specific signaling molecules, thereby exerting regulatory effects on various forms of PCD. ZBP1 is involved in apoptosis, necroptosis, pyroptosis, and PANoptosis and interacts with molecules, such as receptor-interacting protein kinase 3 (RIPK3), to influence cell fate under various pathological conditions. It plays a crucial role in regulating PCD during infections, inflammatory and neurological diseases, cancers, and other conditions, affecting disease onset and progression. Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions. This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD, along with the potential therapeutic implications of ZBP1 in these contexts. Ongoing research on ZBP1 is being refined across various disease models, and these advancements may provide novel insights for studies focusing on PCD, potentially leading to new therapeutic options for related diseases.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

The chemical components of Carthami Flos were investigated by using macroporous resin, silica gel column chromatography, reversed-phase octadecylsilane(ODS) column chromatography, Sephadex LH-20, and semi-preparative high-performance liquid chromatography(HPLC). The planar structures of the compounds were established based on their physicochemical properties and ultraviolet-visible(UV-Vis), infrared(IR), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), and nuclear magnetic resonance(NMR) spectroscopic technology. The absolute configurations were determined by comparing the calculated and experimental electronic circular dichroism(ECD). Six flavonoid C-glycosides were isolated from the 30% ethanol elution fraction of macroporous resin obtained from the 95% ethanol extract of Carthami Flos, and identified as saffloquinoside F(1), 5-hydroxysaffloneoside(2), iso-5-hydroxysaffloneoside(3), isosafflomin C(4), safflomin C(5), and vicenin 2(6). Among these, the compounds 1 to 3 were new chalcone C-glycosides. The compounds 1, 2, 4, and 5 could significantly increase the viability of H9c2 cardiomyocytes damaged by oxygen-glucose deprivation/reoxygenation(OGD/R) at a concentration of 50 μmol·L~(-1), showing their good cardioprotective activity.
Glycosides/pharmacology* ; Flowers/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Carthamus tinctorius/chemistry* ; Chalcones/pharmacology* ; Animals