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1.
Front Neurol ; 15: 1364952, 2024.
Article in English | MEDLINE | ID: mdl-38699054

ABSTRACT

Background: Timely intravenous thrombolysis (IVT) is crucial for improving outcomes in acute ischemic stroke (AIS) patients. This study evaluates the effectiveness of the Acute Stroke Care Map (ASCaM) initiative in Shenyang, aimed at reducing door-to-needle times (DNT) and thus improving the timeliness of care for AIS patients. Methods: An retrospective cohort study was conducted from April 2019 to December 2021 in 30 hospitals participating in the ASCaM initiative in Shenyang. The ASCaM bundle included strategies such as EMS prenotification, rapid stroke triage, on-call stroke neurologists, immediate neuroimaging interpretation, and the innovative Pre-hospital Emergency Call and Location Identification feature. An interrupted time series analysis (ITSA) was used to assess the impact of ASCaM on DNT, comparing 9 months pre-intervention with 24 months post-intervention. Results: Data from 9,680 IVT-treated ischemic stroke patients were analyzed, including 2,401 in the pre-intervention phase and 7,279 post-intervention. The ITSA revealed a significant reduction in monthly DNT by -1.12 min and a level change of -5.727 min post-ASCaM implementation. Conclusion: The ASCaM initiative significantly reduced in-hospital delays for AIS patients, demonstrating its effectiveness as a comprehensive stroke care improvement strategy in urban settings. These findings highlight the potential of coordinated care interventions to enhance timely access to reperfusion therapies and overall stroke prognosis.

2.
Mol Nutr Food Res ; 68(8): e2300720, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38581348

ABSTRACT

SCOPE: The global prevalence of obesity has significantly increased, presenting a major health challenge. High-fat diet (HFD)-induced obesity is closely related to the disease severity of psoriasis, but the mechanism is not fully understood. METHODS AND RESULTS: The study utilizes the HFD-induced obesity model along with an imiquimod (IMQ)-induced psoriasis-like mouse model (HFD-IMQ) to conduct transcriptomics and metabolomic analyses. HFD-induced obese mice exhibits more severe psoriasis-like lesions compared to normal diet (ND)-IMQ mice. The expression of genes of the IL-17 signaling pathway (IL-17A, IL-17F, S100A9, CCL20, CXCL1) is significantly upregulated, leading to an accumulation of T cells and neutrophils in the skin. Moreover, the study finds that there is an inhibition of the branched-chain amino acids (BCAAs) catabolism pathway, and the key gene branched-chain amino transferase 2 (Bcat2) is significantly downregulated, and the levels of leucine, isoleucine, and valine are elevated in the HFD-IMQ mice. Furthermore, the study finds that the peroxisome proliferator-activated receptor gamma (PPAR γ) is inhibited, while STAT3 activity is promoted in HFD-IMQ mice. CONCLUSION: HFD-induced obesity significantly amplifies IL-17 signaling and exacerbates psoriasis, with a potential role played by Bcat2-mediated BCAAs metabolism. The study suggests that BCAA catabolism and PPAR γ-STAT3 exacerbate inflammation in psoriasis with obesity.


Subject(s)
Amino Acids, Branched-Chain , Diet, High-Fat , Obesity , Psoriasis , Transaminases , Animals , Male , Mice , Amino Acids, Branched-Chain/metabolism , Diet, High-Fat/adverse effects , Disease Models, Animal , Imiquimod , Inflammation/metabolism , Interleukin-17/metabolism , Interleukin-17/genetics , Mice, Inbred C57BL , Mice, Obese , Obesity/metabolism , Obesity/complications , PPAR gamma/metabolism , PPAR gamma/genetics , Psoriasis/metabolism , Psoriasis/pathology , Signal Transduction , Skin/metabolism , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , Transaminases/metabolism
3.
Eur J Nucl Med Mol Imaging ; 51(6): 1651-1661, 2024 May.
Article in English | MEDLINE | ID: mdl-38182838

ABSTRACT

PURPOSE: MRI-negative children with focal cortical dysplasia type II (FCD II) are one of the most challenging cases in surgical epilepsy management. We aimed to utilize quantitative positron emission tomography (QPET) analysis to complement [18F]SynVesT-1 and [18F]FDG PET imaging and facilitate the localization of epileptogenic foci in pediatric MRI-negative FCD II patients. METHODS: We prospectively enrolled 17 MRI-negative children with FCD II who underwent [18F]SynVesT-1 and [18F]FDG PET before surgical resection. The QPET scans were analyzed using statistical parametric mapping (SPM) with respect to healthy controls. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of [18F]SynVesT-1 PET, [18F]FDG PET, [18F]SynVesT-1 QPET, and [18F]FDG QPET in the localization of epileptogenic foci were assessed. Additionally, we developed a multivariate prediction model based on dual trace PET/QPET assessment. RESULTS: The AUC values of [18F]FDG PET and [18F]SynVesT-1 PET were 0.861 (sensitivity = 94.1%, specificity = 78.2%, PPV = 38.1%, NPV = 98.9%) and 0.908 (sensitivity = 82.4%, specificity = 99.2%, PPV = 93.3%, NPV = 97.5%), respectively. [18F]FDG QPET showed lower sensitivity (76.5%) and NPV (96.6%) but higher specificity (95.0%) and PPV (68.4%) than visual assessment, while [18F]SynVesT-1 QPET exhibited higher sensitivity (94.1%) and NPV (99.1%) but lower specificity (97.5%) and PPV (84.2%). The multivariate prediction model had the highest AUC value (AUC = 0.996, sensitivity = 100.0%, specificity = 96.6%, PPV = 81.0%, NPV = 100%). CONCLUSIONS: The multivariate prediction model based on [18F]SynVesT-1 and [18F]FDG PET/QPET assessments holds promise in noninvasively identifying epileptogenic regions in MRI-negative children with FCD II. Furthermore, the combination of visual assessment and QPET may improve the sensitivity and specificity of diagnostic tests in localizing epileptogenic foci and achieving a preferable surgical outcome in MRI-negative FCD II.


Subject(s)
Epilepsy , Fluorodeoxyglucose F18 , Magnetic Resonance Imaging , Positron-Emission Tomography , Humans , Child , Male , Female , Positron-Emission Tomography/methods , Child, Preschool , Adolescent , Malformations of Cortical Development, Group I/diagnostic imaging , Focal Cortical Dysplasia
4.
Res Sq ; 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38260621

ABSTRACT

C-H bond activation enables the facile synthesis of new chemicals. While C-H activation in short-chain alkanes has been widely investigated, it remains largely unexplored for long-chain organic molecules. Here, we report light-driven C-H activation in complex organic materials mediated by 2D transition metal dichalcogenides (TMDCs) and the resultant solid-state synthesis of luminescent carbon dots in a spatially-resolved fashion. We unravel the efficient H adsorption and a lowered energy barrier of C-C coupling mediated by 2D TMDCs to promote C-H activation. Our results shed light on 2D materials for C-H activation in organic compounds for applications in organic chemistry, environmental remediation, and photonic materials.

5.
J Ethnopharmacol ; 324: 117714, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38184027

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The inflammatory skin condition psoriasis is immune-related. The decoction of Jianpi-Yangxue-Jiiedu (JPYX) is a useful medication for psoriasis. However, the underlying mechanics of JPYX have not yet been clarified. AIM OF THE STUDY: The objective of this study was to investigate the mechanism underlying the efficacy of JPYX in the treatment of psoriasis in the context of a high-fat diet. MATERIALS AND METHODS: This work generated a high-fat feeding model of imiquimod (IMQ)-induced psoriasis-like lesion mice. The blood composition of JPYX was examined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The mechanism of JPYX decoction for treating psoriasis was predicted using methods of network pharmacology, metabolomics, and transcriptomics. RESULTS: JPYX prevented the release of inflammatory cytokines, decreased keratinocyte proliferation, enhanced the percentage of Treg cells in the skin, lymph nodes, and thymus, and greatly alleviated psoriatic lesions. Network pharmacology predicted that IL-1ß, TNF, STAT3, and EGFR may be potential targets, and KEGG results showed that PI3K-AKT-mTOR may be a potential mechanism of action. Verification of experimental data demonstrated that the JPYX decoction dramatically decreased mTOR and AKT phosphorylation. According to metabolomics analysis, amino acids and their metabolites, benzene and its substitutes, aldehyde ketone esters, heterocyclic compounds, etc. were the primary metabolites regulated by JPYX. KEGG enrichment analysis of differential metabolites was performed. Fatty acid biosynthesis, Type I polyketide structures, Steroid hormone biosynthesis, Biosynthesis of unsaturated fatty acid, etc. Transcriptomic results showed that JPYX significantly regulated skin development, keratinocyte differentiation, and oxidative phosphorylation. Further experimental data verification showed that JPYX decoction significantly reduced the mRNA levels of mt-Nd4, mt-Nd5, mt-Nd1, Ifi205, Ifi211, and mt-Atp8. CONCLUSIONS: JPYX may improve psoriasis by regulating the metabolic pathways of fatty acids and electron transport of oxidative phosphorylation.


Subject(s)
Drugs, Chinese Herbal , Psoriasis , Animals , Mice , Oxidative Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Electron Transport , Phosphatidylinositol 3-Kinases/metabolism , Chromatography, Liquid , Electrons , Tandem Mass Spectrometry , Psoriasis/chemically induced , Psoriasis/drug therapy , Psoriasis/metabolism , TOR Serine-Threonine Kinases/metabolism , Drugs, Chinese Herbal/adverse effects
6.
Eur Radiol ; 34(2): 887-898, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37581655

ABSTRACT

OBJECTIVES: To investigate [18F]FDG PET patterns of mesial temporal lobe epilepsy (MTLE) patients with distinct pathologic types and provide possible guidance for predicting long-term prognoses of patients undergoing epilepsy surgery. METHODS: This was a retrospective review of MTLE patients who underwent anterior temporal lobectomy between 2016 and 2021. Patients were classified as having chronic inflammation and gliosis (gliosis, n = 44), hippocampal sclerosis (HS, n = 43), or focal cortical dysplasia plus HS (FCD-HS, n = 13) based on the postoperative pathological diagnosis. Metabolic patterns and the severity of metabolic abnormalities were investigated among MTLE patients and healthy controls (HCs). The standardized uptake value (SUV), SUV ratio (SUVr), and asymmetry index (AI) of regions of interest were applied to evaluate the severity of metabolic abnormalities. Imaging processing was performed with statistical parametric mapping (SPM12). RESULTS: With a mean follow-up of 2.8 years, the seizure freedom (Engel class IA) rates of gliosis, HS, and FCD-HS were 54.55%, 62.79%, and 69.23%, respectively. The patients in the gliosis group presented a metabolic pattern with a larger involvement of extratemporal areas, including the ipsilateral insula. SUV, SUVr, and AI in ROIs were decreased for patients in all three MTLE groups compared with those of HCs, but the differences among all three MTLE groups were not significant. CONCLUSIONS: MTLE patients with isolated gliosis had the worst prognosis and hypometabolism in the insula, but the degree of metabolic decrease did not differ from the other two groups. Hypometabolic regions should be prioritized for [18F]FDG PET presurgical evaluation rather than [18F]FDG uptake values. CLINICAL RELEVANCE STATEMENT: This study proposes guidance for optimizing the operation scheme in patients with refractory MTLE and emphasizes the potential of molecular neuroimaging with PET using selected tracers to predict the postsurgical histology of patients with refractory MTLE epilepsy. KEY POINTS: • MTLE patients with gliosis had poor surgical outcomes and showed a distinct pattern of decreased metabolism in the ipsilateral insula. • In the preoperative assessment of MTLE, it is recommended to prioritize the evaluation of glucose hypometabolism areas over [18F]FDG uptake values. • The degree of glucose hypometabolism in the epileptogenic focus was not associated with the surgical outcomes of MTLE.


Subject(s)
Epilepsy, Temporal Lobe , Humans , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/surgery , Fluorodeoxyglucose F18 , Gliosis/diagnostic imaging , Positron-Emission Tomography , Glucose , Magnetic Resonance Imaging
7.
Front Neurol ; 14: 1247492, 2023.
Article in English | MEDLINE | ID: mdl-37928151

ABSTRACT

Background: This study aimed to compare the performance of different machine learning models in predicting symptomatic intracranial hemorrhage (sICH) after thrombolysis treatment for ischemic stroke. Methods: This multicenter study utilized the Shenyang Stroke Emergency Map database, comprising 8,924 acute ischemic stroke patients from 29 comprehensive hospitals who underwent thrombolysis between January 2019 and December 2021. An independent testing cohort was further established, including 1,921 patients from the First People's Hospital of Shenyang. The structured dataset encompassed 15 variables, including clinical and therapeutic metrics. The primary outcome was the sICH occurrence post-thrombolysis. Models were developed using an 80/20 split for training and internal validation. Performance was assessed using machine learning classifiers, including logistic regression with lasso regularization, support vector machine (SVM), random forest, gradient-boosted decision tree (GBDT), and multilayer perceptron (MLP). The model boasting the highest area under the curve (AUC) was specifically employed to highlight feature importance. Results: Baseline characteristics were compared between the training cohort (n = 6,369) and the external validation cohort (n = 1,921), with the sICH incidence being slightly higher in the training cohort (1.6%) compared to the validation cohort (1.1%). Among the evaluated models, the logistic regression with lasso regularization achieved the highest AUC of 0.87 (95% confidence interval [CI]: 0.79-0.95; p < 0.001), followed by the MLP model with an AUC of 0.766 (95% CI: 0.637-0.894; p = 0.04). The reference model and SVM showed AUCs of 0.575 and 0.582, respectively, while the random forest and GBDT models performed less optimally with AUCs of 0.536 and 0.436, respectively. Decision curve analysis revealed net benefits primarily for the SVM and MLP models. Feature importance from the logistic regression model emphasized anticoagulation therapy as the most significant negative predictor (coefficient: -2.0833) and recombinant tissue plasminogen activator as the principal positive predictor (coefficient: 0.5082). Conclusion: After a comprehensive evaluation, the MLP model is recommended due to its superior ability to predict the risk of symptomatic hemorrhage post-thrombolysis in ischemic stroke patients. Based on decision curve analysis, the MLP-based model was chosen and demonstrated enhanced discriminative ability compared to the reference. This model serves as a valuable tool for clinicians, aiding in treatment planning and ensuring more precise forecasting of patient outcomes.

8.
Eur J Nucl Med Mol Imaging ; 51(1): 168-179, 2023 12.
Article in English | MEDLINE | ID: mdl-37707571

ABSTRACT

PURPOSE: Temporal lobe epilepsy (TLE) is a common, polygenic epilepsy syndrome that involves glucose hypometabolism in the epileptogenic zone. However, the transcriptional and cellular signatures underlying the metabolism in TLE remain unclear. METHODS: In this retrospective study, 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) scans of TLE patients (n = 104) who underwent anterior temporal lobectomy were consecutively collected between 2016 and 2021. The transcriptional profiles of TLE risk genes across the brain were identified by the gene expression analyses from six TLE patients and twelve postmortem donors (six from the Allen Human Brain Atlas). Integrating the neuroimaging and transcriptomic data, we examined the relationship between the expression of TLE-associated genes and metabolic alterations in TLE. Furthermore, we performed functional enrichment analyses of the genes with higher weight in partial least squares regression using Metascape. RESULTS: A total of 104 patients with TLE (mean age 29 ± 9 years, 50% male) and 30 healthy controls (HCs) (mean age 31 ± 6 years, 53% male) were enrolled. Compared to that of HCs, patients with TLE showed hypometabolism in the temporal lobes and adjacent structures but hypermetabolism in the thalamus and basal ganglia. The cortical map of inter-group differences in cerebral metabolism was spatially correlated with the expression of a weighted combination of genes enriched in ontology terms and pathways related to neurovascular unit (NVU) integrity and synaptic plasticity. DISCUSSION: Our findings, combined with the analysis of neuroimaging and transcriptional data, suggest that genes related to NVU integrity and synaptic plasticity may drive alterations to brain metabolism that mediate the genetic risk of TLE.


Subject(s)
Epilepsy, Temporal Lobe , Humans , Male , Young Adult , Adult , Female , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/genetics , Retrospective Studies , Brain/diagnostic imaging , Brain/metabolism , Temporal Lobe/diagnostic imaging , Temporal Lobe/metabolism , Positron-Emission Tomography/methods , Fluorodeoxyglucose F18/metabolism , Glucose/metabolism , Magnetic Resonance Imaging
9.
J Inflamm Res ; 16: 3823-3836, 2023.
Article in English | MEDLINE | ID: mdl-37667801

ABSTRACT

Purpose: Resveratrol (Res) is a natural polyphenol with anti-inflammatory and immunomodulatory effects. Alterations in metabolic pathways have been studied in psoriasis. This study is aimed to further explore the potential molecular mechanism of psoriasis improvement by Res. Patients and Methods: Imiquimod (IMQ)-induced psoriasis-like mouse model was established to observe the effects of Res. NanoString nCounter Metabolic Pathways Panel was used to analyze the changed mRNA and qRT-PCR was used for validation. Flow cytometry was used to analyze immune cell subsets in skin lesions. In vitro, we observed the effects of Res on R848-stimulated macrophages glycolysis and inflammation. Results: Res reduced the proliferation of keratinocytes and the secretion of inflammatory cytokines in IMQ-induced psoriasis-like mouse model. Psoriasis model skin lesions were in a state of hypoxia, with upregulated glycolysis and downregulated AMPK activity. Res inhibited the levels of hypoxia-related genes (hif1α, hif3α) and glycolysis-related genes (hk1, ldha), meanwhile increased the levels of AMPK genes (prkaa1, prkaa2). Flow cytometry analysis revealed that Res decreased the infiltration of macrophages in psoriasis-like lesions. In addition, Res decreased the secretion of macrophage-associated pro-inflammatory cytokines (IL-23, TNF-α, IL-1ß). In vitro, Res diminished the secretion of IL-23, TNF-α, IL-1ß, and lactate by R848-stimulated macrophages and activated AMPK. Conclusion: This study suggested that Res diminished psoriasis symptoms by inhibiting macrophages infiltration and inhibiting glycolysis, which providing novel insights into the underlying mechanisms of therapeutic action of Res in the treatment of psoriasis.

10.
Nat Nanotechnol ; 18(11): 1295-1302, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37500779

ABSTRACT

Epitaxial growth of two-dimensional transition metal dichalcogenides on sapphire has emerged as a promising route to wafer-scale single-crystal films. Steps on the sapphire act as sites for transition metal dichalcogenide nucleation and can impart a preferred domain orientation, resulting in a substantial reduction in mirror twins. Here we demonstrate control of both the nucleation site and unidirectional growth direction of WSe2 on c-plane sapphire by metal-organic chemical vapour deposition. The unidirectional orientation is found to be intimately tied to growth conditions via changes in the sapphire surface chemistry that control the step edge location of WSe2 nucleation, imparting either a 0° or 60° orientation relative to the underlying sapphire lattice. The results provide insight into the role of surface chemistry on transition metal dichalcogenide nucleation and domain alignment and demonstrate the ability to engineer domain orientation over wafer-scale substrates.

11.
CNS Neurosci Ther ; 29(9): 2656-2665, 2023 09.
Article in English | MEDLINE | ID: mdl-37017415

ABSTRACT

AIMS: Differentiating mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE) remains challenging. Our study characterized the metabolic profiles between MTLE and NTLE and their correlation with surgical prognosis using 18 F-FDG-PET. METHODS: A total of 137 patients with intractable temporal lobe epilepsy (TLE) and 40 age-matched healthy controls were recruited. Patients were divided into the MTLE group (N = 91) and the NTLE group (N = 46). 18 F-FDG-PET was used to measure the metabolism of regional cerebra, which was analyzed using statistical parametric mapping. The volume of abnormal metabolism in cerebral regions and their relationship with surgical prognosis were calculated for each surgical patient. RESULTS: The cerebral hypometabolism of MTLE was limited to the ipsilateral temporal and insular lobes (p < 0.001, uncorrected). The NTLE patients showed hypometabolism in the ipsilateral temporal, frontal, and parietal lobes (p < 0.001, uncorrected). The MTLE patients showed extensive hypermetabolism in cerebral regions (p < 0.001, uncorrected). Hypermetabolism in NTLE was limited to the contralateral temporal lobe and cerebellum, ipsilateral frontal lobe, occipital lobe, and bilateral thalamus (p < 0.001, uncorrected). Among patients who underwent resection of epileptic lesions, 51 (67.1%) patients in the MTLE group and 10 (43.5%) in the NTLE group achieved Engel class IA outcome (p = 0.041). The volumes of metabolic increase for the frontal lobe or thalamus in the MTLE group were larger in non-Engel class IA patients than Engel class IA patients (p < 0.05). CONCLUSIONS: The spatial metabolic profile discriminated NTLE from MTLE. Hypermetabolism of the thalamus and frontal lobe in MTLE may facilitate preoperative counseling and surgical planning.


Subject(s)
Epilepsy, Temporal Lobe , Neocortex , Humans , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/surgery , Epilepsy, Temporal Lobe/metabolism , Neocortex/diagnostic imaging , Neocortex/surgery , Fluorodeoxyglucose F18 , Treatment Outcome , Metabolome , Positron-Emission Tomography , Hippocampus/metabolism
12.
Eur Radiol ; 33(5): 3396-3406, 2023 May.
Article in English | MEDLINE | ID: mdl-36692596

ABSTRACT

OBJECTIVES: To determine whether fructose-1,6-bisphosphatase 1 (FBP1) expression is associated with [18F]FDG PET uptake and postsurgical outcomes in patients with mesial temporal lobe epilepsy (mTLE) and to investigate whether the molecular mechanism involving gamma-aminobutyric acid type A receptor (GABAAR), glucose transporter-3 (GLUT-3), and hexokinase-II (HK-II). METHODS: Forty-three patients with mTLE underwent [18F]FDG PET/CT. Patients were divided into Ia (Engel class Ia) and non-Ia (Engel class Ib-IV) groups according to more than 1 year of follow-up after surgery. The maximum standard uptake value (SUVmax) and asymmetry index (AI) of hippocampus were measured. The relationship among the SUVmax, AI, prognosis, and FBP1 expression was analyzed. A lithium-pilocarpine acute mTLE rat model was subjected to [18F]FDG micro-PET/CT. Hippocampal SUVmax and FBP1, GABAAR, GLUT-3, and HK-II expression were analyzed. RESULTS: SUVmax was higher in the Ia group than in the non-Ia group (7.31 ± 0.97 vs. 6.56 ± 0.96, p < 0.05) and FBP1 expression was lower in the Ia group (0.24 ± 0.03 vs. 0.27 ± 0.03, p < 0.01). FBP1 expression was negatively associated with SUVmax and AI (p < 0.01). In mTLE rats, the hippocampal FBP1 increased (0.26 ± 0.00 vs. 0.17 ± 0.00, p < 0.0001), and SUVmax, GLUT-3 and GABAAR levels decreased significantly (0.73 ± 0.12 vs. 1.46 ± 0.23, 0.20 ± 0.01 vs. 0.32 ± 0.05, 0.26 ± 0.02 vs. 0.35 ± 0.02, p < 0.05); no significant difference in HK-II levels was observed. In mTLE patients and rats, FBP1 negatively correlated with SUVmax and GLUT-3 and GABAAR levels (p < 0.05). CONCLUSION: FBP1 expression was inversely associated with SUVmax in mTLE, which might inhibit [18F]FDG uptake by regulating GLUT-3 expression. High FBP1 expression was indicative of low GABAAR expression and poor prognosis. KEY POINTS: • It is of paramount importance to explore the deep pathophysiological mechanisms underlying the pathogenesis of mesial temporal lobe epilepsy and find potential therapeutic targets. • [18F]FDG PET has demonstrated low metabolism in epileptic regions during the interictal period, and hypometabolism may be associated with prognosis, but the pathomechanism of this association remains uncertain. • Our results support the possibility that FBP1 might be simultaneously involved in the regulation of glucose metabolism levels and the excitability of neurons and suggest that targeting FBP1 may be a viable strategy in the diagnosis and treatment of mesial temporal lobe epilepsy.


Subject(s)
Epilepsy, Temporal Lobe , Fluorodeoxyglucose F18 , Animals , Rats , Fluorodeoxyglucose F18/metabolism , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/pathology , Fructose-Bisphosphatase/metabolism , Positron Emission Tomography Computed Tomography , Prognosis , Positron-Emission Tomography/methods , gamma-Aminobutyric Acid
13.
Phytochemistry ; 208: 113585, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36693580

ABSTRACT

Nine undescribed phloroglucinol derivatives (dryatraols A-I) with five different backbones and three known dimeric acylphloroglucinols were isolated from the rhizome of Dryopteris atrata (Wall. Ex Kunze) Ching (Dryopteridaceae). Dryatraol A contains an unprecedented carbon skeleton-a butyrylphloroglucinol and a rulepidanol-type sesquiterpene are linked via a furan ring to form a 6/5/6/6 ring system. Dryatraols B and C are the first examples of monomeric phloroglucinols coupled with the aristolane-type sesquiterpene through the C-C bond. Dryatraol D features a rare spiro [benzofuran-2',5″-furan] backbone. Dryatraols E-I are five undescribed adducts with a butyrylphloroglucinol or filicinic acid incorporated into the germacrene-type sesquiterpene via a pyran ring. These undescribed structures were determined by comprehensively analysing the spectroscopic data, X-ray diffraction results, and electronic circular dichroism calculations. The result of in vitro antiviral activity evaluation indicated that dryatraol C displayed the strongest antiviral effect against both respiratory syncytial virus and influenza A virus (H1N1), with IC50 values of 11.9 µM and 5.5 µM, respectively. Dryatraols F-H exhibited considerable inhibitory activity against herpes simplex virus type 1 (HSV-1), with IC50 values ranging from 2.6 to 6.3 µM. Analysis of the inhibitory mechanism using a time-of-addition assay revealed that dryatraol G may inhibit the replication of HSV-1 by interfering with the late stage of the viral life cycle.


Subject(s)
Dryopteris , Herpesvirus 1, Human , Influenza A Virus, H1N1 Subtype , Dryopteris/chemistry , Phloroglucinol , Antiviral Agents/chemistry , Furans/pharmacology , Molecular Structure
14.
J Burn Care Res ; 44(3): 715-722, 2023 May 02.
Article in English | MEDLINE | ID: mdl-32006002

ABSTRACT

The aim of the study was to investigate the effects of the rhGM-CSF gel on third-degree frostbite wounds. Sixty-two patients who had suffered third-degree frostbite on their hand or foot (91 wounds in total) were selected using a convenience sampling method and randomly allocated to two groups: the rhGM-CSF group(31patients,45 frostbite wounds) received the rhGM-CSF gel when wound dressing change daily; however, the control group (31patients, 46 frostbite wounds) received aloe glue. The wound healing time, the score of inflammation about the wound and the positive bacterial culture of wound secretions were used to measure outcomes, respectively. Data were analyzed using SPSS (25.0), Student's t test or Mann-Whitney U test and chi-square test or Fisher exact test were selected, as appropriate. The healing time of the rhGM-CSF group was (12.2 ± 5.0) days, which was significantly shorter than that of the control group (15.5 ± 4.7) days (P < .0001). The rhGM-CSF group's wound inflammation scores on the 7th and 14th day of treatment were (0.96 ± 0.21) and (1.88 ± 0.29), respectively, which were better than those of the control group (1.12 ± 0.24) and (1.38 ± 0.15) (both P < .0001). The positive bacterial culture of wound secretions in the rhGM-CSF group was also better than that in the control group on the 3rd, 7th, and 14th day after treatment (P = .027, .004, .030, respectively). According to the results, using rhGM-CSF gel considerably increases the speed of frostbite wounds healing, and have an effect on protecting third-degree frostbite wounds regarding the positive effects. Trial Registration: This trial was registered in the Chinese Clinical Trial Register, ChiCTR1900021299.


Subject(s)
Burns , Frostbite , Humans , Burns/drug therapy , Recombinant Proteins/therapeutic use , Frostbite/drug therapy , China , Inflammation
15.
Nat Prod Res ; 37(15): 2551-2558, 2023.
Article in English | MEDLINE | ID: mdl-35319320

ABSTRACT

One new alkaloid, 6, 7-dimethoxyisoquinoline-N-oxide (1), one new benzofuran derivative, 3,7-dimethyl-6-acetyl-8-benzofuranol (2) and one new lignan, salsolains A (3), along with seven known compounds (4-10), were isolated from the whole plant of Salsola collina Pall. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HR-ESI-MS, 1 D and 2 D NMR), and their absolute configurations were determined by the X-ray crystallography and ECD calculation. The activities of compounds 1-10 against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were assessed, especially, compound 5 (50 µM) exhibited the most significant anti-inflammatory activity with the secretion levels of IL-6 and TNF-α at 3.87% and 4.03%, respectively.


Subject(s)
Alkaloids , Salsola , Animals , Mice , Salsola/chemistry , Tumor Necrosis Factor-alpha , Interleukin-6 , Macrophages , RAW 264.7 Cells , Molecular Structure
16.
Front Neurol ; 14: 1330959, 2023.
Article in English | MEDLINE | ID: mdl-38249750

ABSTRACT

Background: Acute Ischemic Stroke (AIS) presents significant challenges in evaluating the effectiveness of Endovascular Treatment (EVT). This study develops a novel prognostic model to predict 6-month mortality post-EVT, aiding in identifying patients likely to benefit less from this intervention, thus enhancing therapeutic decision-making. Methods: We employed a cohort of AIS patients from Shenyang First People's Hospital, serving as the Validation set, to develop our model. LASSO regression was used for feature selection, followed by logistic regression to create a prognostic nomogram for predicting 6-month mortality post-EVT. The model's performance was validated using a dataset from PLA Northern Theater Command General Hospital, assessing discriminative ability (C-index), calibration (calibration plot), and clinical utility (decision curve analysis). Statistical significance was set at p < 0.05. Results: The development cohort consisted of 219 patients. Six key predictors of 6-month mortality were identified: "Lack of Exercise" (OR, 4.792; 95% CI, 1.731-13.269), "Initial TICI Score 1" (OR, 1.334; 95% CI, 0.628-2.836), "MRS Score 5" (OR, 1.688; 95% CI, 0.754-3.78), "Neutrophil Percentage" (OR, 1.08; 95% CI, 1.042-1.121), "Onset Blood Sugar" (OR, 1.119; 95% CI, 1.007-1.245), and "Onset NIHSS Score" (OR, 1.074; 95% CI, 1.029-1.121). The nomogram demonstrated a high predictive capability with a C-index of 0.872 (95% CI, 0.830-0.911) in the development set and 0.830 (95% CI, 0.726-0.920) in the validation set. Conclusion: Our nomogram, incorporating factors such as Lack of Exercise, Initial TICI Score 1, MRS Score 5, Neutrophil Percentage, Onset Blood Sugar, and Onset NIHSS Score, provides a valuable tool for predicting 6-month mortality in AIS patients post-EVT. It offers potential to refine early clinical decision-making and optimize patient outcomes, reflecting a shift toward more individualized patient care.

17.
ACS Nano ; 16(6): 9651-9659, 2022 Jun 28.
Article in English | MEDLINE | ID: mdl-35621266

ABSTRACT

Two-dimensional chalcogenide semiconductors have recently emerged as a host material for quantum emitters of single photons. While several reports on defect- and strain-induced single-photon emission from 2D chalcogenides exist, a bottom-up, lithography-free approach to producing a high density of emitters remains elusive. Further, the physical properties of quantum emission in the case of strained 2D semiconductors are far from being understood. Here, we demonstrate a bottom-up, scalable, and lithography-free approach for creating large areas of localized emitters with high density (∼150 emitters/um2) in a WSe2 monolayer. We induce strain inside the WSe2 monolayer with high spatial density by conformally placing the WSe2 monolayer over a uniform array of Pt nanoparticles with a size of 10 nm. Cryogenic, time-resolved, and gate-tunable luminescence measurements combined with near-field luminescence spectroscopy suggest the formation of localized states in strained regions that emit single photons with a high spatial density. Our approach of using a metal nanoparticle array to generate a high density of strained quantum emitters will be applied to scalable, tunable, and versatile quantum light sources.

18.
Front Immunol ; 13: 897835, 2022.
Article in English | MEDLINE | ID: mdl-35619697

ABSTRACT

Background: Autophagy has been proven to play an important role in the pathogenesis of asthma and the regulation of the airway epithelial immune microenvironment. However, a systematic analysis of the clinical importance of autophagy-related genes (ARGs) regulating the immune microenvironment in patients with asthma remains lacking. Methods: Clustering based on the k-means unsupervised clustering method was performed to identify autophagy-related subtypes in asthma. ARG-related diagnostic markers in low-autophagy subtypes were screened, the infiltration of immune cells in the airway epithelium was evaluated by the CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. On the basis of the expression of ARGs and combined with asthma control, a risk prediction model was established and verified by experiments. Results: A total of 66 differentially expressed ARGs and 2 subtypes were identified between mild to moderate and severe asthma. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes, and the low-autophagy subtype was closely associated with severe asthma, energy metabolism, and hormone metabolism. The autophagy gene SERPINB10 was identified as a diagnostic marker and was related to the infiltration of immune cells, such as activated mast cells and neutrophils. Combined with asthma control, a risk prediction model was constructed, the expression of five risk genes was supported by animal experiments, was established for ARGs related to the prediction model. Conclusion: Autophagy plays a crucial role in the diversity and complexity of the asthma immune microenvironment and has clinical value in treatment response and prognosis.


Subject(s)
Asthma , Serpins , Animals , Asthma/etiology , Autophagy/genetics , Autophagy-Related Protein 5/genetics , Epithelium/metabolism , Humans , Prognosis
19.
Front Neurol ; 13: 838222, 2022.
Article in English | MEDLINE | ID: mdl-35359644

ABSTRACT

Corona Virus Disease 2019 (COVID-19), the novel coronavirus disease, is now a global pandemic. Vaccination can significantly reduce the mortality rate caused by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). There are currently several effective vaccines that have been introduced. Inactivated COVID-19 vaccine is one of these options and is generally considered safe. Neurofascin (NF) plays an important role in keeping the functionality of the node of Ranvier. We report here a rare case of anti-NF186+ chronic inflammatory demyelinating polyneuropathy (CIDP) in a 23-year-old male patient who was vaccinated with inactivated COVID-19 vaccine prior to the onset. This report adds a new possible rare side effect of a COVID-19 vaccine and provides a case for the clinical effectiveness of rituximab (RTX) in patients with anti-NF186+ CIDP.

20.
Front Aging Neurosci ; 14: 849774, 2022.
Article in English | MEDLINE | ID: mdl-35360210

ABSTRACT

Objective: The features of cerebral metabolism associated with loss of consciousness in patients with temporal lobe epilepsy (TLE) have not been fully elucidated. We aim to investigate the alterations in cortical-subcortical metabolism in temporal lobe epilepsy with impaired awareness seizures (IAS). Methods: Regional cerebral metabolism was measured using fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with TLE-IAS and healthy controls. All patients had a comprehensive evaluation to confirm their seizure origin and lateralization. Videos of all seizures were viewed and rated by at least two epileptologists to identify the state of consciousness when a seizure occurred. By synthesizing the seizure history, semeiology, and video EEG of all patients, as long as the patients had one seizure with impaired awareness, she/he will be included. 76 patients with TLE-IAS and 60 age-matched healthy controls were enrolled in this study. Regional cerebral metabolic patterns were analyzed for TLE-IAS and healthy control groups using statistical parametric mapping. Besides, we compared the MRI-negative patients and MRI-positive patients with healthy controls, respectively. Results: There were no significant differences in the age and sex of TLE-IAS patients and healthy control. TLE-IAS patients showed extensive bilateral hypermetabolism in the frontoparietal regions, cingulate gyrus, corpus callosum, occipital lobes, basal ganglia, thalamus, brainstem, and cerebellum. The region of metabolic change was more extensive in right TLE-IAS than that of the left, including extensive hypometabolism in the ipsilateral temporal, frontal, parietal, and insular lobes. And contralateral temporal lobe, bilateral frontoparietal regions, occipital lobes, the anterior and posterior regions of the cingulate gyrus, bilateral thalamus, bilateral basal ganglia, brainstem, and bilateral cerebellum showed hypermetabolism. The TLE patients with impaired awareness seizure showed hypermetabolism in the cortical-subcortical network including the arousal system. Additionally, 48 MRI-positive and 28 MRI-negative TLE-IAS patients were included in our study. TLE-IAS patients with MRI-negative and MRI-positive were both showed hypermetabolism in the cingulate gyrus. Hypometabolism in the bilateral temporal lobe was showed in the TLE-IAS with MRI-positive. Conclusion: These findings suggested that the repetitive consciousness impairing ictal events may have an accumulative effect on brain metabolism, resulting in abnormal interictal cortical-subcortical metabolic disturbance in TLE patients with impaired awareness seizure. Understanding these metabolic mechanisms may guide future clinical treatments to prevent seizure-related awareness deficits and improve quality of life in people with TLE.

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