Puerarin Alleviates Experimental Autoimmune Thyroiditis by Regulating Macrophages.

Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease, predominantly affecting women. Although the pathogenesis of HT is incompletely understood, some studies have found that macrophage polarization plays a role. Puerarin is a soy isoflavone compound that has anti-inflammatory and immunomodulatory effects and regulates macrophage immune activity. This study aimed to verify the therapeutic effect of puerarin on HT and explored its regulatory effect on macrophage polarization imbalance in HT. Through bioinformatics analysis and molecular biology methods, it was found that macrophages increased significantly in HT patients and model mice. Immunological staining showed that puerarin intervention could reduce tissue inflammatory cell infiltration. Molecular biological examination displayed that puerarin could inhibit local and systemic inflammation levels, and the expression of marker thyroglobulin and thyroid peroxidase Abs. In vivo experimental results indicated that puerarin regulated macrophage polarity and reduced inflammatory damage, possibly by inhibiting the pyroptosis signaling pathway. In vivo macrophage clearance experiments demonstrated that puerarin relied on macrophages to exert its mechanism of action in treating HT. The results of this study indicate that macrophages are important mediators in the development of HT, and puerarin can regulate macrophage polarity and inflammatory status to provide thyroid tissue protection, which provides a new idea for the treatment of HT.

Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and identified as a potential therapeutic target.

Immunotherapy of PD-L1/PD-1 blockage elicited impressive clinical benefits for cancer treatment. However, the relative low response and therapy resistance highlight the need to better understand the molecular regulation of PD-L1 in tumors. Here, we report that PD-L1 is a target of UFMylation. UFMylation of PD-L1 destabilizes PD-L1 by synergizing its ubiquitination. Inhibition of PD-L1 UFMylation via silencing of UFL1 or Ubiquitin-fold modifier 1 (UFM1), or the defective UFMylation of PD-L1, stabilizes the PD-L1 in multiple human and murine cancer cells, and undermines antitumor immunity in vitro and mice, respectively. Clinically, UFL1 expression was decreased in multiple cancers and lower expression of UFL1 negatively correlated with the response of anti-PD1 therapy in melanoma patients. Moreover, we identified a covalent inhibitor of UFSP2 that promoted the UFMylation activity and contributed to the combination therapy with PD-1 blockade. Our findings identified a previously unrecognized regulator of PD-L1 and highlighted UFMylation as a potential therapeutic target.

W2V-repeated index: Prediction of enhancers and their strength based on repeated fragments.

Enhancers are crucial in gene expression regulation, dictating the specificity and timing of transcriptional activity, which highlights the importance of their identification for unravelling the intricacies of genetic regulation. Therefore, it is critical to identify enhancers and their strengths. Repeated sequences in the genome are repeats of the same or symmetrical fragments. There has been a great deal of evidence that repetitive sequences contain enormous amounts of genetic information. Thus, We introduce the W2V-Repeated Index, designed to identify enhancer sequence fragments and evaluates their strength through the analysis of repeated K-mer sequences in enhancer regions. Utilizing the word2vector algorithm for numerical conversion and Manta Ray Foraging Optimization for feature selection, this method effectively captures the frequency and distribution of K-mer sequences. By concentrating on repeated K-mer sequences, it minimizes computational complexity and facilitates the analysis of larger K values. Experiments indicate that our method performs better than all other advanced methods on almost all indicators.

Flexophotovoltaic Effect and Above-Band-Gap Photovoltage Induced by Strain Gradients in Halide Perovskites.

We have measured the flexophotovoltaic effect of single crystals of halide perovskites MAPbBr_{3} and MAPbI_{3}, as well as the benchmark oxide perovskite SrTiO_{3}. For halide perovskites, the flexophotovoltaic effect is found to be orders of magnitude larger than for SrTiO_{3}, and indeed large enough to induce photovoltages bigger than the band gap. Moreover, we find that in MAPbI_{3} the flexophotovoltaic effect is additional to a native bulk photovoltaic response that is switchable and ferroelectric-like. The results suggest that strain gradient engineering can be a powerful tool to modify the photovoltaic output even in already well-established photovoltaic materials.

Antibacterial, Fatigue-Resistant, and Self-Healing Dressing from Natural-Based Composite Hydrogels for Infected Wound Healing.

The treatment of infected wounds faces substantial challenges due to the high incidence and serious infection-related complications. Natural-based hydrogel dressings with favorable antibacterial properties and strong applicability are urgently needed. Herein, we developed a composite hydrogel by constructing multiple networks and loading ciprofloxacin for infected wound healing. The hydrogel was synthesized via a Schiff base reaction between carboxymethyl chitosan and oxidized sodium alginate, followed by the polymerization of the acrylamide monomer. The resultant hydrogel dressing possessed a good self-healing ability, considerable compression strength, and reliable compression fatigue resistance. In vitro assessment showed that the composite hydrogel effectively eliminated bacteria and exhibited an excellent biocompatibility. In a model of Staphylococcus aureus-infected full-thickness wounds, wound healing was significantly accelerated without scars through the composite hydrogel by reducing wound inflammation. Overall, this study opens up a new way for developing multifunctional hydrogel wound dressings to treat wound infections.

Genetic characteristic of mumps virus from 2012 to 2016 and its serum antibody level among general healthy population during 2018-2020 in Jiangsu Province, China.

Mumps is a vaccine-preventable disease with high contagious capability. Its incidence declined rapidly since one dose of mumps vaccine was introduced into Expanded Program of Immunization (EPI) in 2008 in China. Nonetheless, the outbreaks of mumps remain frequent in China. Here we aim to assess herd immunity level followed by one-dose mumps ingredient vaccine and to elucidate the genetic characteristics of mumps viruses circulating in the post vaccine era in Jiangsu province of China. The complete sequences of mumps virus small hydrophobic(SH) gene were amplified and sequenced; coalescent-based Bayesian method was used to perform phylogenetic analysis with BEAST 1.84 software. Commercially available indirect enzyme-linked immune-sorbent IgG assay was used for the quantitative detection of IgG antibody against mumps virus. Our results show that genotype F was the predominant mumps viruses and belonged to indigenous spread, and most of Jiangsu sequences clustered together and formed a monophyly. The prevalence of mumps reached a peak in 2012 and subsequently declined, which presented an obvious different trajectory with virus circulating in other regions of China. The gene diversity of viruses circulating in Jiangsu province was far less than those in China. The antibody prevalence reached 70.42% in the general population during 2018 to 2020. The rising trend of antibody level was also observed. Although mumps antibody prevalence does not reach expected level, mumps virus faces higher pressure in Jiangsu province than the whole of China. To reduce further the prevalence of mumps viruses, two doses of mumps vaccine should be involved into EPI.

Analysis of Imprecision for Internal Quality Control of Newborn Screening by Tandem Mass Spectrometry in China, 2015 - 2021.

BACKGROUND: This study aimed to assess the performance of the newborn screening laboratories in China through retrospective analysis of the coefficient of variation (CV) of the internal quality control (IQC) data in the national tandem mass spectrometry screening for inherited metabolic disorders in newborns. METHODS: From 2015 to 2021, the IQC data of amino acid and acylcarnitine test were collected twice each year. CVmonthly in-control was calculated by excluding outliers for the current month and its discrete distribution and changes in trend were comprehensively evaluated for both normal and high concentration levels. The proportion of laboratories meeting both 1/3 and 1/4 quality criteria of the total error allowable (TEa), based on the CVmonthly in-control for each testing item, was calculated. RESULTS: The analysis of CVmonthly in-control for the two concentration levels for the amino acids and acylcarnitine parameters showed that CVmonthly in-control for the normal concentration levels were more discrete before 2018, while CVmonthly in-control for the high concentration levels were less discrete than the normal concentration levels, but there were relatively more outliers. More than 80% of laboratories were able to meet the 1/3 TEa standard for each test at the high concentration level, while the pass rate for the 1/4 TEa standard was significantly lower than 80% (except for C2). CONCLUSIONS: According to the current status of testing in China, it is recommended to use 1/3TEa as the imprecision level standard; for laboratories with relatively high precision, the 1/4TEa standard can be used.

Result of a Pilot External Quality Assessment Scheme for Clinical Diagnosis of Inherited Metabolic Disorders in China.

BACKGROUND: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice. METHODS: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline. RESULTS: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory. CONCLUSIONS: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.

Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

AXIN1/MYC Axis Mediated the Osimertinib Resistance in EGFR Mutant Non-Small Cell Lung Cancer Cells.

Osimertinib, a promising and approved third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is a standard strategy for EGFR-mutant non-small cell lung cancer (NSCLC) patients. However, developed resistance is unavoidable, which reduces its long-term effectiveness. In this study, RNA sequencing was performed to analyze differentially expressed genes (DEGs). The PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to identify the key genes for clinical prognosis and gene correlation respectively. Protein expression was determined by western blot analysis. Cell viability assay and Ki67 staining were used to evaluate the effect of osimertinib on tumor cells. Finally, we screened out two hub genes, myelocytomatosis oncogene (Myc) and axis inhibition protein 1 (Axin1), upregulated in three osimertinib-resistant cell lines through RNA sequencing and bioinformatics analysis. Next, cell experiment confirmed that expression of C-MYC and AXIN1 were elevated in different EGFR mutant NSCLC cell lines with acquired resistance to osimertinib, compared with their corresponding parental cell lines. Furthermore, we demonstrated that AXIN1 upregulated the expression of C-MYC and mediated the acquired resistance of EGFR mutant NSCLC cells to osimertinib in vitro. In conclusion, AXIN1 affected the sensitivity of EGFR mutant NSCLC to osimertinib via regulating C-MYC expression in vitro. Targeting AXIN1/MYC signaling may be a potential new strategy for overcoming acquired resistance to osimertinib.

A new intestinal supplement 'Synbiotics' therapeutically regulates gut microbiota and activates PPARs pathway to inhibit Alzheimer's disease progression in mouse models.

We aimed to investigate the role of Synbiotic preparations on the interaction of gut microbiota with AD development. APP/PS1 mice were randomized into APP/PS1 and Synbiotics groups, and C57BL/6J mice were used as wild type (WT) control group. The mice in the Synbiotics group and the APP/PS1 group were given Synbiotics and xylo-oligosaccharides for 3 months, respectively. The mice in the WT group were given the same amount of normal saline. Cognitive function was measured. Positron emission computed tomography/magnetic resonance imaging (PET/MRI) was used to detect fasting blood glucose level. Immunohistochemical assay, ELISA, western blot and qRT-PCR were carried out to detect inflammatory factors. DNA extraction of fecal sample was performed to carry out sequencing. Bioinformatics analysis, metabolites sample preparation and Liquid Chromatograph Mass Spectrometer (LC/MS) analysis were also performed. Synbiotics treatment can significantly ameliorate learning and memory competence by inhibiting Aß protein deposition. Different bacteria in the intestine were significantly improved and changes in gut microbiota can affect the intestinal metabolism to affect multiple potential pathways after Synbiotics treatment. Synbiotics treatment can activate peroxisome proliferator activated receptor (PPARs) signaling pathway and significantly reduce neuroinflammation in APP/PS1 mice brains. Synbiotics treatment can effectively reduce neuro-inflammatory response through the regulation of intestinal microflora to delay AD development.

Inversion Method for Chlorophyll-a Concentration in High-Salinity Water Based on Hyperspectral Remote Sensing Data.

As one of the important lakes in the "One Lake and Two Seas" of the Inner Mongolia Autonomous Region, the monitoring of water quality in Lake Daihai has attracted increasing attention, and the concentration of chlorophyll-a directly affects the water quality, making the monitoring of chlorophyll-a concentration in Lake Daihai particularly crucial. Traditional methods of monitoring chlorophyll-a concentration are not only inefficient but also require significant human and material resources. Remote sensing technology has the advantages of wide coverage and short update cycles. For lakes such as Daihai with a high salinity content, salinity is considered a key factor when inverting the concentration of chlorophyll-a. In this study, machine learning models, including model stacking from ensemble learning, a ridge regression model, and a random forest model, were constructed. After comparing the training accuracy of the three models on Zhuhai-1 satellite data, the random forest model, which had the highest accuracy, was selected as the final training model. By comparing the accuracy changes before and after adding salinity factors to the random forest model, a high-precision model for inverting chlorophyll-a concentration in hypersaline lakes was obtained. The research results show that, without considering the salinity factor, the root mean square error (RMSE) of the model was 0.056, and the coefficient of determination (R2) was 0.64, indicating moderate model performance. After adding the salinity factor, the model accuracy significantly improved: the RMSE decreased to 0.047, and the R2 increased to 0.92. This study provides a solid basis for the application of remote sensing technology in hypersaline aquatic environments, confirming the importance of considering salinity when estimating chlorophyll-a concentration in hypersaline waters. This research helps us gain a deeper understanding of the water quality and ecosystem evolution in Daihai Lake.

Remote Sensing Monitoring of Grassland Locust Density Based on Machine Learning.

The main aim of this study was to utilize remote sensing data to establish regression models through machine learning to predict locust density in the upcoming year. First, a dataset for monitoring grassland locust density was constructed based on meteorological data and multi-source remote sensing data in the study area. Subsequently, an SVR (support vector regression) model, BP neural network regression model, random forest regression model, BP neural network regression model with the PCA (principal component analysis), and deep belief network regression model were built on the dataset. The experimental results show that the random forest regression model had the best prediction performance among the five models. Specifically, the model achieved a coefficient of determination (R2) of 0.9685 and a root mean square error (RMSE) of 1.0144 on the test set, which were the optimal values achieved among all the models tested. Finally, the locust density in the study area for 2023 was predicted and, by comparing the predicted results with actual measured data, it was found that the prediction accuracy was high. This is of great significance for local grassland ecological management, disaster warning, scientific decision-making support, scientific research progress, and sustainable agricultural development.

The Origin and Course of the Blood Supply to the Lower Eyelid Orbital Fat: Anatomical Study and Clinical Significance.

PURPOSE: The aim of this study is to investigate the origin and course of the orbital fat arterial supply in the lower eyelid using traditional anatomy and three-dimensional computed tomography (CT). METHODS: Twenty-seven cadaver heads were infused with mercury sulfide contrast media through the ophthalmic artery, maxillary artery, transverse facial artery, and facial artery. CT images were obtained after contrast agent injection, three-dimensional CT scans were reconstructed, and the cadaver heads were dissected. RESULTS: Forty-five qualified hemifaces showed that the orbital fat arterial supply in the lower eyelid originates primarily from the inferomedial muscular trunk (IMT) of the ophthalmic artery and the orbital branch of the infraorbital artery. The medial branch of the IMT terminated at the medial fat pad (35.6%) or the orbital floor (64.4%). The lateral branch terminated at the inferior oblique (IO) muscle (28.9%) or the central and lateral fat pads (17.8%). In 53.3%, the lateral branch extended to the anterior part of the lateral fat pad and terminated in the orbital wall or the zygomaticoorbital foramina. The orbital branch of the infraorbital artery coursed between the orbital floor and the orbital fat, providing supply to the IO muscle, inferior rectus (IR) muscle, nasolacrimal duct, and orbital fat. CONCLUSION: This study elucidated the origin and course of the orbital fat arterial supply in the lower eyelid, which may help to avoid reducing the blood supply of the orbital fat pedicles during surgery. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Molecular Insights into the Specific Targeting of c-MYC G-Quadruplex by Thiazole Peptides.

Stabilization of a G-quadruplex (G4) in the promotor of the c-MYC proto-oncogene leads to inhibition of gene expression, and it thus represents a potentially attractive new strategy for cancer treatment. However, most G4 stabilizers show little selectivity among the many G4s present in the cellular complement of DNA and RNA. Intriguingly, a crescent-shaped cell-penetrating thiazole peptide, TH3, preferentially stabilizes the c-MYC G4 over other promotor G4s, but the mechanisms leading to this selective binding remain obscure. To investigate these mechanisms at the atomic level, we performed an in silico comparative investigation of the binding of TH3 and its analogue TH1 to the G4s from the promotors of c-MYC, c-KIT1, c-KIT2, and BCL2. Molecular docking and molecular dynamics simulations, combined with in-depth analyses of non-covalent interactions and bulk and per-nucleotide binding free energies, revealed that both TH3 and TH1 can induce the formation of a sandwich-like framework through stacking with both the top and bottom G-tetrads of the c-MYC G4 and the adjacent terminal capping nucleotides. This framework produces enhanced binding affinities for c-MYC G4 relative to other promotor G4s, with TH3 exhibiting an outstanding binding priority. Van der Waals interactions were identified to be the key factor in complex formation in all cases. Collectively, our findings fully agree with available experimental data. Therefore, the identified mechanisms leading to specific binding of TH3 towards c-MYC G4 provide valuable information to guide the development of new selective G4 stabilizers.

Coupled relationships between landscape pattern and ecosystem health in response to urbanization.

Rapid urbanization has highlighted ecological problems in the metropolitan area, with increasing landscape fragmentation and severe threats to ecosystem health (EH). Studying the spatio-temporal coupled relationship between landscape pattern and EH and its response to urbanization in the Fuzhou metropolitan area (FMA) can provide scientific reference for its long-term development planning. We examined the coupled relationship between landscape pattern and EH and its driving mechanism in the FMA at grid and township scales to address the gap. The results show that landscape heterogeneity, diversity, and dispersion are gradually increasing, and EH is rising progressively in the FMA from 2000 to 2020. The spatial distribution of landscape pattern indices and EH indicators showed a "high in the south and low in the north" trend. During the study period, the coupled relationship between landscape patterns and EH was increasingly powerful but with remarkable spatial heterogeneity. The study also found an inverted U-shaped relationship between urbanization and coupled relationships. Ecological landscapes' heterogeneity, diversity, and connectivity in low-urbanization areas are conducive to EH. The opposite is true for high-urbanization areas. This study provides a valuable reference for optimizing landscape planning and ecological management in metropolitan areas.

In Silico Investigations on the Synergistic Binding Mechanism of Functional Compounds with Beta-Lactoglobulin.

Piceatannol (PIC) and epigallocatechin gallate (EGCG) are polyphenolic compounds with applications in the treatment of various diseases such as cancer, but their stability is poor. ß-lactoglobulin (ß-LG) is a natural carrier that provides a protective effect to small molecule compounds and thus improves their stability. To elucidate the mechanism of action of EGCG, PIC, and palmitate (PLM) in binding to ß-LG individually and jointly, this study applied molecular docking and molecular dynamics simulations combined with in-depth analyses including noncovalent interaction (NCI) and binding free energy to investigate the binding characteristics between ß-LG and compounds of PIC, EGCG, and PLM. Simulations on the binary complexes of ß-LG + PIC, ß-LG + EGCG, and ß-LG + PLM and ternary complexes of (ß-LG + PLM) + PIC, (ß-LG + PLM) + EGCG, ß-LG + PIC) + EGCG, and (ß-LG + EGCG) + PIC were performed for comparison and characterizing the interactions between binding compounds. The results demonstrated that the co-bound PIC and EGCG showed non-beneficial effects on each other. However, the centrally located PLM was revealed to be able to adjust the binding conformation of PIC, which led to the increase in binding affinity with ß-LG, thus showing a synergistic effect on the co-bound PIC. The current study of ß-LG co-encapsulated PLM and PIC provides a theoretical basis and research suggestions for improving the stability of polyphenols.

Assessing the data quality of AdHawk MindLink eye-tracking glasses.

Most commercially available eye-tracking devices rely on video cameras and image processing algorithms to track gaze. Despite this, emerging technologies are entering the field, making high-speed, cameraless eye-tracking more accessible. In this study, a series of tests were conducted to compare the data quality of MEMS-based eye-tracking glasses (AdHawk MindLink) with three widely used camera-based eye-tracking devices (EyeLink Portable Duo, Tobii Pro Glasses 2, and SMI Eye Tracking Glasses 2). The data quality measures assessed in these tests included accuracy, precision, data loss, and system latency. The results suggest that, overall, the data quality of the eye-tracking glasses was lower compared to that of a desktop EyeLink Portable Duo eye-tracker. Among the eye-tracking glasses, the accuracy and precision of the MindLink eye-tracking glasses were either higher or on par with those of Tobii Pro Glasses 2 and SMI Eye Tracking Glasses 2. The system latency of MindLink was approximately 9 ms, significantly lower than that of camera-based eye-tracking devices found in VR goggles. These results suggest that the MindLink eye-tracking glasses show promise for research applications where high sampling rates and low latency are preferred.

Recycling alkali lignin-derived biochar with adsorbed cadmium into cost-effective CdS/C photocatalyst for methylene blue removal.

Cadmium (Cd)-enriched adsorbents wastes possess great environmental risk due to their large-scale accumulation and toxicity in the natural environment. Recycling spent Cd-enriched adsorbents into efficient catalysts for advanced applications could address the environmental issues and attain the carbon neutral goal. Herein, a facile strategy is developed for the first time to reutilize the alkali lignin (AL)-derived biochar (ALB) absorbed with Cd into cadmium sulphide (CdS)/C composite for the efficient methylene blue (MB) removal. The ALB is initially treated with Cd-containing solution, then the recycling ALB samples with adsorbed Cd are converted to the final CdS/C composite using NaS2 as the sulphurizing reagent for vulcanization reaction. The optimal ALB400 demonstrates a high adsorption capacity of 576.0 mg g-1 for Cd removal. Then the converted CdS/C composite shows an efficient MB removal efficiency of 94%. The photodegradation mechanism is mainly attributed to carbon components in the CdS/C composite as electron acceptor promoting the separation of photoelectrons/holes and slowing down the abrasion of CdS particles. The enhanced charge transfer and contact between the carrier and the active site thus improves the removal performance and reusability. This work not only develops a method for removing Cd from wastewater effectively and achieving the waste resource utilization but also further offers a significant guidance to use other kinds of spent heavy metal removal adsorbents for the construction of low-cost and high value-added functional materials.

[Effects of tetramethylpyrazine on pharmacokinetics in plasma and brain dialysate and neuropathic pain in rat model of spared sciatic nerve injury].

This study aims to explore the effects of tetramethylpyrazine(TMP) on pharmacokinetics in plasma and brain dialysate and neuropathic pain in the rat model of partial sciatic nerve injury(SNI), and to investigate the correlation between the analgesic effect of TMP and its concentrations in the plasma and brain dialysate. Male SD rats were randomized into Sham, SNI, and SNI+TMP groups. Mechanical stimulation with von frey filaments and cold spray method were employed to evaluate the mechanical sensitivity and cold sensitivity of rats. Another two groups, Sham+TMP and SNI+TMP, were used to intubate the common jugular vein and implant microdialysis probes into the anterior cingulate gyrus(ACC), respectively.After intraperitoneal injection of TMP at a dose of 80 mg·kg~(-1), automatic blood collection and intracerebral microdialysis(perfusion rate of 1 µL·min~(-1)) systems were used to collect the blood and brain dialysate for 24 h. HSS T3 C_(18) reversed-phase chromatographic column(2.1 mm×50 mm, 2.5 µm) was used for liquid chromatographic separation. Gradient elution was carried out with the mobile phase of methanol-water(containing 0.005% formic acid) at a flow rate of 0.25 mL·min~(-1). Electrospray ion source was used for mass spectrometry, and the scanning mode was multi-reaction monitoring under the positive ion mode. The ion pairs for quantitative analysis were TMP m/z 137/122 and aspirin m/z 179/137, respectively. DAS 2.11 was used to calculate the pharmacokinetic parameters. The optimal time of TMP to exert the analgesia effect and inhibit cold pain sensitivity was 60 min after treatment. The TMP in the plasma and brain dialysate of SNI rats showed the T_(max) of 15 min and 30 min, the C_(max) of(2 866.43±135.39) and(1 462.14±197.38) µg·L~(-1), the AUC_(0-t) of(241 463.30±28 070.31) and(213 115.62±32 570.07) µg·min·L~(-1), the MRT_(0-t) of(353.13±47.73) and(172.16±12.72) min, and the CL_Z of 0.73 and 0.36 L·min·kg~(-1), respectively. The analgesic effect of TMP had a significant correlation with the blood drug concentration in the ACC, which indicated that this method was suitable for the detection of TMP in rat plasma and brain dialysate. The method is accurate, reliable, and sensitive and can realize the important value of the application of correlation analysis theory of "automatic blood collection-microdialysis/PK-PD" in the research on neuropathic pain.