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1.
Opt Express ; 32(10): 16809-16822, 2024 May 06.
Article En | MEDLINE | ID: mdl-38858878

The X-ray sources for Compton radiography of ICF experiments are generated by using intense picosecond lasers to irradiate wire targets. The wire diameter must be designed thin enough, for example ∼ 10 µm in many published works, to comply a high spatial resolution. This results in a low laser-target interception, which limits the photon yield. We investigated a technique of coded-source radiography based on laser-driven annular sources via Monte Carlo and PIC simulations. The annular X-ray source is formed by laser irradiating tube target in which the effect of electron recirculation plays an important role. We proved that this technique has an increased spatial resolution and contrast than that using the Gaussian source produced by wire targets. Therefore, the diameter of the backlighter target can be significantly increased to uplift laser-target interception without compromising on spatial resolution. This contributes towards a reconciliation between the spatial resolution and photon yield for Compton radiography. The results predict the possibility of improving source photon yield by several times in future experiments.

2.
Opt Express ; 32(9): 15065-15077, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38859166

Optical resonators made of 2D photonic crystal (PhC) slabs provide efficient ways to manipulate light at the nanoscale through small group-velocity modes with low radiation losses. The resonant modes in periodic photonic lattices are predominantly limited by nonleaky guided modes at the boundary of the Brillouin zone below the light cone. Here, we propose a mechanism for ultra-high Q resonators based on the bound states in the continuum (BICs) above the light cone that have zero-group velocity (ZGV) at an arbitrary Bloch wavevector. By means of the mode expansion method, the construction and evolution of avoided crossings and Friedrich-Wintgen BICs are theoretically investigated at the same time. By tuning geometric parameters of the PhC slab, the coalescence of eigenfrequencies for a pair of BIC and ZGV modes is achieved, indicating that the waveguide modes are confined longitudinally by small group-velocity propagation and transversely by BICs. Using this mechanism, we engineer ultra-high Q nanoscale resonators that can significantly suppress the radiative losses, despite the operating frequencies above the light cone and the momenta at the generic k point. Our work suggests that the designed devices possess potential applications in low-threshold lasers and enhanced nonlinear effects.

4.
Nat Plants ; 2024 May 21.
Article En | MEDLINE | ID: mdl-38773271

The nuclear pore complex (NPC) is vital for nucleocytoplasmic communication. Recent evidence emphasizes its extensive association with proteins of diverse functions, suggesting roles beyond cargo transport. Yet, our understanding of NPC's composition and functionality at this extended level remains limited. Here, through proximity-labelling proteomics, we uncover both local and global NPC-associated proteome in Arabidopsis, comprising over 500 unique proteins, predominantly associated with NPC's peripheral extension structures. Compositional analysis of these proteins revealed that the NPC concentrates chromatin remodellers, transcriptional regulators and mRNA processing machineries in the nucleoplasmic region while recruiting translation regulatory machinery on the cytoplasmic side, achieving a remarkable orchestration of the genetic information flow by coupling RNA transcription, maturation, transport and translation regulation. Further biochemical and structural modelling analyses reveal that extensive interactions with nucleoporins, along with phase separation mediated by substantial intrinsically disordered proteins, may drive the formation of the unexpectedly large nuclear pore proteome assembly.

5.
Eur J Med Chem ; 272: 116426, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38718622

Pyruvate kinase isoform 2 (PKM2) is closely related to the regulation of Th17/Treg balance, which is considered to be an effective strategy for UC therapy. Parthenolide (PTL), a natural product, only possesses moderate PKM2-activating activity. Thus, five series of PTL derivatives are designed and synthesized to improve PKM2-activated activities and anti-UC abilities. Through detailed structure optimization, B4 demonstrates potent T-cell anti-proliferation activity (IC50 = 0.43 µM) and excellent PKM2-activated ability (AC50 = 0.144 µM). Subsequently, through mass spectrometry analysis, B4 is identified to interact with Cys423 of PKM2 via covalent-bond. Molecular docking and molecular dynamic simulation results reveal that the trifluoromethoxy of B4 forms a stronger hydrophobic interaction with Ala401, Pro402, and Ile403. In addition, B4 has a significant effect only on Th17 cell differentiation, thereby regulating the Th17/Treg balance. The effect of B4 on Th17/Treg imbalance can be attributed to inhibition of PKM2 dimer translocation and suppression of glucose metabolism. Finally, B4 can notably ameliorate the symptoms of dextran sulfate sodium (DSS)-induced colitis in mouse model in vivo. Thus, B4 is confirmed as a potent PKM2 activator, and has the potential to develop as a novel anti-UC agent.


Colitis, Ulcerative , Drug Design , Lactones , Pyruvate Kinase , Sesquiterpenes , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/chemical synthesis , Animals , Mice , Pyruvate Kinase/metabolism , Pyruvate Kinase/antagonists & inhibitors , Lactones/pharmacology , Lactones/chemistry , Lactones/chemical synthesis , Structure-Activity Relationship , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Humans , Molecular Structure , Cell Proliferation/drug effects , Mice, Inbred C57BL , Dose-Response Relationship, Drug , Male , Dextran Sulfate , Molecular Docking Simulation , Thyroid Hormones/metabolism , Th17 Cells/drug effects , Thyroid Hormone-Binding Proteins
6.
Front Pharmacol ; 15: 1366529, 2024.
Article En | MEDLINE | ID: mdl-38711993

Introduction: It is known that patients with immune-abnormal co-pregnancies are at a higher risk of adverse pregnancy outcomes. Traditional pregnancy risk management systems have poor prediction abilities for adverse pregnancy outcomes in such patients, with many limitations in clinical application. In this study, we will use machine learning to screen high-risk factors for miscarriage and develop a miscarriage risk prediction model for patients with immune-abnormal pregnancies. This model aims to provide an adjunctive tool for the clinical identification of patients at high risk of miscarriage and to allow for active intervention to reduce adverse pregnancy outcomes. Methods: Patients with immune-abnormal pregnancies attending Sichuan Provincial People's Hospital were collected through electronic medical records (EMR). The data were divided into a training set and a test set in an 8:2 ratio. Comparisons were made to evaluate the performance of traditional pregnancy risk assessment tools for clinical applications. This analysis involved assessing the cost-benefit of clinical treatment, evaluating the model's performance, and determining its economic value. Data sampling methods, feature screening, and machine learning algorithms were utilized to develop predictive models. These models were internally validated using 10-fold cross-validation for the training set and externally validated using bootstrapping for the test set. Model performance was assessed by the area under the characteristic curve (AUC). Based on the best parameters, a predictive model for miscarriage risk was developed, and the SHapley additive expansion (SHAP) method was used to assess the best model feature contribution. Results: A total of 565 patients were included in this study on machine learning-based models for predicting the risk of miscarriage in patients with immune-abnormal pregnancies. Twenty-eight risk warning models were developed, and the predictive model constructed using XGBoost demonstrated the best performance with an AUC of 0.9209. The SHAP analysis of the best model highlighted the total number of medications, as well as the use of aspirin and low molecular weight heparin, as significant influencing factors. The implementation of the pregnancy risk scoring rules resulted in accuracy, precision, and F1 scores of 0.3009, 0.1663, and 0.2852, respectively. The economic evaluation showed a saving of ¥7,485,865.7 due to the model. Conclusion: The predictive model developed in this study performed well in estimating the risk of miscarriage in patients with immune-abnormal pregnancies. The findings of the model interpretation identified the total number of medications and the use of other medications during pregnancy as key factors in the early warning model for miscarriage risk. This provides an important basis for early risk assessment and intervention in immune-abnormal pregnancies. The predictive model developed in this study demonstrated better risk prediction performance than the Pregnancy Risk Management System (PRMS) and also demonstrated economic value. Therefore, miscarriage risk prediction in patients with immune-abnormal pregnancies may be the most cost-effective management method.

8.
J Exp Bot ; 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38655916

Endocytic recycling is an intracellular trafficking pathway that returns endocytosed molecules to the plasma membrane (PM) via the recycling endosome. This pathway plays a crucial role in remodeling PM composition and is thus essential for normal cellular homeostasis. In plants, endocytic recycling regulates the localization and abundance of receptors, transporters, and channels at the PM that are involved in many aspects of plant growth and development. Despite its importance, the recycling endosome and the underlying sorting mechanisms for cargo recycling in plants remain understudied in comparison to the endocytic recycling pathways of animal systems. In this review, we focus on the cumulative evidence suggesting the existence of endosomes decorated by regulators that contribute to recycling in plant cells. We summarize the chemical inhibitors used for analyzing cargo recycling and discuss recent advances in our understanding of how endocytic recycling participates in various plant cellular and physiological events.

9.
J Hazard Mater ; 470: 134205, 2024 May 15.
Article En | MEDLINE | ID: mdl-38579583

Carbazole (CBZ) and acridine (ACR) are polycyclic aromatic nitrogen heterocycles (PANHs) widely found in combined contaminated soils, while investigations on organic-organic interactions have been very limited. In this study, batch experiments were carried out on five soils with different properties, taking CBZ as a representative of PANHs and ACR as a co-existing contaminant. The adsorption isotherms of CBZ (50-1000 µg/L) were nonlinear. Soil organic matter (SOM) and cation exchange capacity (CEC) showed positive correlations with CBZ adsorption-desorption coefficients. The adsorption mechanisms of CBZ involved hydrogen bonding, π-π interaction, and cation-π bonding. Different concentrations of ACR had varying effects on CBZ. The adsorption of CBZ was inhibited with 250 µg/L ACR. The cooperative adsorption was observed on three soils with increasing ACR concentration (1000 µg/L) and led to more pronounced nonlinear isotherms. The S-shaped isotherms of ACR indicated that ACR was adsorbed to the soil surface in a perpendicular configuration. New adsorption sites were created allowing for increased CBZ adsorption through π-π interaction with ACR. Therefore, variations in soil properties and potential impacts of co-existing contaminants should be well considered when assessing the combined pollution of site soil. This will contribute to a more accurate estimation of environmental and health risks.

10.
Risk Manag Healthc Policy ; 17: 1053-1067, 2024.
Article En | MEDLINE | ID: mdl-38680477

Purpose: This study provides a reference for healthcare organizations in the selection and rational use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition). Methods: According to the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition) released in 2023, relevant databases such as PubMed, Cochrane, and Embase, drug labels, and clinical guidelines were searched for drug information. We systematically evaluated 7 GLP-1RAs marketed in China for safety, efficacy, economy, pharmacological properties, and other attributes using a percentage scoring method. Results: The final assessment result scores from highest to lowest were semaglutide (71.5 points), dulaglutide (68.9 points), liraglutide (68.7 points), exenatide (62.5 points), lixisenatide (59.9 points), polyethylene glycol loxenatide (55.9 points), and benaglutide (45.1 points). Conclusion: When a healthcare organization introduces GLP-1RAs to their hospital, they can refer to the assessment results and use the top three recommended medications: semaglutide, dulaglutide, and liraglutide.

11.
J Vasc Access ; : 11297298241244483, 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38682422

BACKGROUND: The mortality is significantly higher in patients undergoing maintenance hemodialysis (MHD) than in the general population. It is well-known that vascular access (VA) is critical for MHD patients. But the association between VA satisfaction and all-cause mortality in MHD patients is still not clear. The aim of this study was to explore the relationship between VA satisfaction and all-cause mortality in MHD patients with a 30-month follow-up. METHODS: Two hundred twenty-nine MHD patients in two dialysis centers were enrolled in this observational prospective study. VA satisfaction was assessed using the Short Form Vascular Access Questionnaire (VAQ). Health-related quality of life (HRQoL) score was calculated with Short Form 36 (SF-36) questionnaire. Multiple logistic regression analysis was used to evaluate the influencing factors of all-cause mortality. RESULTS: During the 30-month follow-up period, 35 patients dropped out of the study. Among them, 31 patients died, and 4 patients stopped MHD treatment after renal transplantation. Multivariable analyses showed that the age, VAQ total score, social functioning score and dialysis-related complication score of the VAQ, the total score and MCS of the SF-36 were factors influencing all-cause mortality in MHD patients. The Kaplan-Meier curve further showed that the cumulative survival probability was significantly higher in the MHD patients with VAQ scores <7 at baseline than in patients with VAQ scores ⩾7 (p = 0.031). INCLUSION: The present study showed that VA satisfaction was significantly associated with all-cause mortality in MHD patients. These findings suggest that a holistic approach is required for VA choice.

12.
Front Psychiatry ; 15: 1352971, 2024.
Article En | MEDLINE | ID: mdl-38563026

Background: No consistent conclusion has been reached regarding the attentional bias characteristics of adolescents with major depressive disorders (MDD), and unexamined co-occurring anxiety distress may contribute to this inconsistency. Methods: We enrolled 50 MDD adolescents with anxiety distress, 47 MDD adolescents without anxiety distress and 48 healthy adolescents. We measured attentional bias using a point-probe paradigm during a negative-neutral emotional face task. Reaction time, correct response rate and attentional bias value were measured. Results: MDD adolescents did not show a negative attentional bias; MDD adolescents with anxiety distress exhibited longer reaction time for negative and neutral stimuli, lower correct response rate for negative stimuli. Hamilton Anxiety Scale scores were positively correlated with reaction time, negatively correlated with correct response rate, and not significantly correlated with attentional bias value. Limitations: The cross-sectional design hinders causal attribution, and positive emotional faces were not included in our paradigm. Conclusion: Negative attentional bias is not a stable cognitive trait in adolescents with MDD, and avoidance or difficulty in disengaging attention from negative emotional stimuli may be the attentional bias characteristic of MDD adolescents with anxiety distress.

13.
Small Methods ; : e2400007, 2024 Apr 04.
Article En | MEDLINE | ID: mdl-38573877

The development of non-precious hydrogen oxidation reaction (HOR) catalysts is a major challenge for the commercialization of Pt-free fuel cells. Herein, a temperature-induced phase hybridization method is reported that greatly improves the catalytic performance of NiCu alloy for the HOR. The migration of W atoms hybridizes the interface of tungsten oxide (WOx) and tungsten carbide (WC) at the onset reduction temperature of WOx, leading to a greatly weakened H binding energy and an optimized OH binding energy, which endows NiCuW/WOx-WC@WC with favorable stability and CO resistance during HOR. The hybridization catalysts deliver a high mass activity of 29.37 mA mg-1 Ni and reach a peak power of 298 mW.cm-2 in H2-O2 anion exchange membrane fuel cells (AEMFCs).

14.
Front Pharmacol ; 15: 1372973, 2024.
Article En | MEDLINE | ID: mdl-38606176

Objective: Aloperine (ALO) is an effective quinolizidine alkaloid. Previous research has demonstrated its antiarrhythmic effect by inhibiting voltage-gated sodium currents in rat ventricular myocytes. This study explored its effect on transient outward potassium currents (Ito) in rat atrial myocytes to identify potential targets in the context of ion channel currents. Methods: The Ito characteristics in rat atrial myocytes were recorded using a whole-cell patch-clamp technique. Molecular docking was performed to validate ligand-protein binding interactions. Results: ALO at concentrations of 3 and 10 µM significantly reduced Ito current densities. Gating kinetics analysis revealed ALO's ability to slow Ito activation, hasten inactivation, and prolong transition from inactive to resting state. Molecular docking revealed that ALO could stably bind to KCND2. Conclusion: ALO may inhibit Ito by slowing the activation process, accelerating inactivation, and delaying the recovery time after inactivation, potentially preventing acetylcholine-induced AF.

15.
Plant Cell Rep ; 43(4): 88, 2024 Mar 10.
Article En | MEDLINE | ID: mdl-38461436

KEY MESSAGE: The homolog gene of the Growth Arrest and DNA Damage-inducible 45 (GADD45) in rice functions in the regulation of plant architecture, grain yield, and blast resistance. The Growth Arrest and DNA Damage-inducible 45 (GADD45) family proteins, well-established stress sensors and tumor suppressors in mammals, serve as pivotal regulators of genotoxic stress responses and tumorigenesis. In contrast, the homolog and role of GADD45 in plants have remained unclear. Herein, using forward genetics, we identified an activation tagging mutant AC13 exhibited dwarf characteristics resulting from the loss-of-function of the rice GADD45α homolog, denoted as OsGADD45a1. osgadd45a1 mutants displayed reduced plant height, shortened panicle length, and decreased grain yield compared to the wild-type Kitaake. Conversely, no obvious differences in plant height, panicle length, or grain yield were observed between wild-type and OsGADD45a1 overexpression plants. OsGADD45a1 displayed relatively high expression in germinated seeds and panicles, with localization in both the nucleus and cytoplasm. RNA-sequencing analysis suggested a potential role for OsGADD45a1 in the regulation of photosynthesis, and binding partner identification indicates OsGADD45a1 interacts with OsRML1 to regulate rice growth. Intriguingly, our study unveiled a novel role for OsGADD45a1 in rice blast resistance, as osgadd45a1 mutant showed enhanced resistance to Magnaporthe oryzae, and the expression of OsGADD45a1 was diminished upon blast fungus treatment. The involvement of OsGADD45a1 in rice blast fungus resistance presents a groundbreaking finding. In summary, our results shed light on the multifaceted role of OsGADD45a1 in rice, encompassing biotic stress response and the modulation of several agricultural traits, including plant height, panicle length, and grain yield.


Oryza , Plant Proteins , Plant Proteins/metabolism , Edible Grain/genetics , Seeds/genetics , Seeds/metabolism , Oryza/metabolism , Plant Diseases/genetics , Plant Diseases/microbiology , Gene Expression Regulation, Plant
16.
Int J Mol Sci ; 25(6)2024 Mar 19.
Article En | MEDLINE | ID: mdl-38542412

Thousands of lncRNAs have been found in zebrafish embryogenesis and adult tissues, but their identification and organogenesis-related functions have not yet been elucidated. In this study, high-throughput sequencing was performed at three different organogenesis stages of zebrafish embryos that are important for zebrafish muscle development. The three stages were 10 hpf (hours post fertilization) (T1), 24 hpf (T2), and 36 hpf (T3). LncRNA gas5, associated with muscle development, was screened out as the next research target by high-throughput sequencing and qPCR validation. The spatiotemporal expression of lncRNA gas5 in zebrafish embryonic muscle development was studied through qPCR and in situ hybridization, and functional analysis was conducted using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9, CRISPR/Cas9). The results were as follows: (1) A total of 1486 differentially expressed lncRNAs were identified between T2 and T1, among which 843 lncRNAs were upregulated and 643 were downregulated. The comparison with T3 and T2 resulted in 844 differentially expressed lncRNAs, among which 482 lncRNAs were upregulated and 362 lncRNAs were downregulated. A total of 2137 differentially expressed lncRNAs were found between T3 and T1, among which 1148 lncRNAs were upregulated and 989 lncRNAs were downregulated, including lncRNA gas5, which was selected as the target gene. (2) The results of spatiotemporal expression analysis showed that lncRNA gas5 was expressed in almost all detected embryos of different developmental stages (0, 2, 6, 10, 16, 24, 36, 48, 72, 96 hpf) and detected tissues of adult zebrafish. (3) After lncRNA gas5 knockout using CRISPR/Cas9 technology, the expression levels of detected genes related to muscle development and adjacent to lncRNA gas5 were more highly affected in the knockout group compared with the control group, suggesting that lncRNA gas5 may play a role in embryonic muscle development in zebrafish. (4) The results of the expression of the skeletal myogenesis marker myod showed that the expression of myod in myotomes was abnormal, suggesting that skeletal myogenesis was affected after lncRNA gas5 knockout. The results of this study provide an experimental basis for further studies on the role of lncRNA gas5 in the embryonic skeletal muscle development of zebrafish.


RNA, Long Noncoding , Animals , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Zebrafish/metabolism , Organogenesis/genetics , Embryonic Development/genetics , Muscle Development/genetics
17.
World J Clin Oncol ; 15(2): 243-270, 2024 Feb 24.
Article En | MEDLINE | ID: mdl-38455128

BACKGROUND: The development and progression of hepatocellular carcinoma (HCC) have been reported to be associated with immune-related genes and the tumor microenvironment. Nevertheless, there are not enough prognostic biomarkers and models available for clinical use. Based on seven prognostic genes, this study calculated overall survival in patients with HCC using a prognostic survival model and revealed the immune status of the tumor microenvironment (TME). AIM: To develop a novel immune cell-related prognostic model of HCC and depict the basic profile of the immune response in HCC. METHODS: We obtained clinical information and gene expression data of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. TCGA and ICGC datasets were used for screening prognostic genes along with developing and validating a seven-gene prognostic survival model by weighted gene coexpression network analysis and least absolute shrinkage and selection operator regression with Cox regression. The relative analysis of tumor mutation burden (TMB), TME cell infiltration, immune checkpoints, immune therapy, and functional pathways was also performed based on prognostic genes. RESULTS: Seven prognostic genes were identified for signature construction. Survival receiver operating characteristic curve analysis showed the good performance of survival prediction. TMB could be regarded as an independent factor in HCC survival prediction. There was a significant difference in stromal score, immune score, and estimate score between the high-risk and low-risk groups stratified based on the risk score derived from the seven-gene prognostic model. Several immune checkpoints, including VTCN1 and TNFSF9, were found to be associated with the seven prognostic genes and risk score. Different combinations of checkpoint blockade targeting inhibitory CTLA4 and PD1 receptors and potential chemotherapy drugs hold great promise for specific HCC therapies. Potential pathways, such as cell cycle regulation and metabolism of some amino acids, were also identified and analyzed. CONCLUSION: The novel seven-gene (CYTH3, ENG, HTRA3, PDZD4, SAMD14, PGF, and PLN) prognostic model showed high predictive efficiency. The TMB analysis based on the seven genes could depict the basic profile of the immune response in HCC, which might be worthy of clinical application.

18.
Brain Imaging Behav ; 2024 Mar 21.
Article En | MEDLINE | ID: mdl-38512647

Previous studies have provided evidence of structural and functional changes in the brains of patients with tension-type headache (TTH). However, investigations of functional connectivity alterations in TTH have been inconclusive. The present study aimed to investigate abnormal intrinsic functional connectivity patterns in patients with TTH through the voxel-wise degree centrality (DC) method as well as functional connectivity (FC) analysis. A total of 33 patients with TTH and 30 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and were enrolled in the final study. The voxel-wise DC method was performed to quantify abnormalities in the local functional connectivity hubs. Nodes with abnormal DC were used as seeds for further FC analysis to evaluate alterations in functional connectivity patterns. In addition, correlational analyses were performed between abnormal DC and FC values and clinical features. Compared with HCs, patients with TTH had higher DC values in the left middle temporal gyrus (MTG.L) and lower DC values in the left anterior cingulate and paracingulate gyri (ACG.L) (GRF, voxel-wise p < 0.05, cluster-wise p < 0.05, two-tailed). Seed-based FC analyses revealed that patients with TTH showed greater connections between ACG.L and the right cerebellum lobule IX (CR-IX.R), and smaller connections between ACG.L and ACG.L. The MTG.L showed increased FC with the ACG.L, and decreased FC with the right caudate nucleus (CAU.R) and left precuneus (PCUN.L) (GRF, voxel-wise p < 0.05, cluster-wise p < 0.05, two-tailed). Additionally, the DC value of the MTG.L was negatively correlated with the DASS-depression score (p = 0.046, r=-0.350). This preliminary study provides important insights into the pathophysiological mechanisms of TTH.

19.
Brain Res ; 1838: 148889, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38552934

Table tennis training has been employed as an exercise treatment to enhance cognitive brain functioning in patients with mental illnesses. However, research on its underlying mechanisms remains limited. In this study, we investigated functional and structural changes in large-scale brain regions between 20 table tennis players (TTPs) and 21 healthy controls (HCs) using 7-Tesla magnetic resonance imaging (MRI) techniques. Compared with those of HCs, TTPs exhibited significantly greater fractional anisotropy (FA) and axial diffusivity (AD) values in multiple fiber tracts. We used the locations with the most significant structural changes in white matter as the seed areas and then compared static and dynamic functional connectivity (sFC and dFC). Brodmann 11, located in the orbitofrontal cortex, showed altered dFC values to large-scale brain regions, such as the occipital lobe, thalamus, and cerebellar hemispheres, in TTPs. Brodmann 48, located in the temporal lobe, showed altered dFC to the parietal lobe, frontal lobe, cerebellum, and occipital lobe. Furthermore, the AD values of the forceps minor (Fmi) and right anterior thalamic radiations (ATRs) were negatively correlated with useful field of view (UFOV) test scores in TTPs. Our results suggest that table tennis players exhibit a unique pattern of dynamic neural activity, this provides evidence for potential mechanisms through which table tennis interventions can enhance attention and other cognitive functions.


Brain , Magnetic Resonance Imaging , White Matter , Humans , White Matter/physiology , White Matter/diagnostic imaging , Male , Brain/physiology , Young Adult , Adult , Magnetic Resonance Imaging/methods , Female , Diffusion Tensor Imaging/methods , Neural Pathways/physiology
20.
Eur J Nucl Med Mol Imaging ; 51(8): 2308-2319, 2024 Jul.
Article En | MEDLINE | ID: mdl-38467921

PURPOSE: Chimeric antigen receptor (CAR) T-cell therapy has been confirmed to benefit patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL). It is important to provide precise and timely predictions of the efficacy and toxicity of CAR T-cell therapy. In this study, we evaluated the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) combining with clinical indices and laboratory indicators in predicting outcomes and toxicity of anti-CD19 CAR T-cell therapy for DLBCL patients. METHODS: Thirty-eight DLBCL patients who received CAR T-cell therapy and underwent [18F]FDG PET/CT within 3 months before (pre-infusion) and 1 month after CAR T-cell infusion (M1) were retrospectively reviewed and regularly followed up. Maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV), clinical indices, and laboratory indicators were recorded at pre-infusion and M1 time points, and changes in these indices were calculated. Progression-free survival (PFS) and overall survival (OS) were as endpoints. Based on the multivariate Cox regression analysis, two predictive models for PFS and OS were developed and evaluated the efficiency. Pre-infusion indices were subjected to predict the grade of cytokine release syndrome (CRS) resulting from toxic reactions. RESULTS: For survival analysis at a median follow-up time of 18.2 months, patients with values of international prognostic index (IPI), SUVmax at M1, and TLG at M1 above their optimal thresholds had a shorter PFS (median PFS: 8.1 months [IPI ≥ 2] vs. 26.2 months [IPI < 2], P = 0.025; 3.1 months [SUVmax ≥ 5.69] vs. 26.8 months [SUVmax < 5.69], P < 0.001; and 3.1 months [TLG ≥ 23.79] vs. 26.8 months [TLG < 23.79], P < 0.001). In addition, patients with values of SUVmax at M1 and ∆SUVmax% above their optimal thresholds had a shorter OS (median OS: 12.6 months [SUVmax ≥ 15.93] vs. 'not reached' [SUVmax < 15.93], P < 0.001; 32.5 months [∆SUVmax% ≥ -46.76] vs. 'not reached' [∆SUVmax% < -46.76], P = 0.012). Two novel predictive models for PFS and OS were visualized using nomogram. The calibration analysis and the decision curves demonstrated good performance of the models. Spearman's rank correlation (rs) analysis revealed that the CRS grade correlated strongly with the pre-infusion SUVmax (rs = 0.806, P < 0.001) and moderately with the pre-infusion TLG (rs = 0.534, P < 0.001). Multinomial logistic regression analysis revealed that the pre-infusion value of SUVmax correlated with the risk of developing a higher grade of CRS (P < 0.001). CONCLUSION: In this group of DLBCL patients who underwent CAR T-cell therapy, SUVmax at M1, TLG at M1, and IPI were independent risk factors for PFS, and SUVmax at M1 and ∆SUVmax% for OS. Based on these indicators, two novel predictive models were established and verified the efficiency for evaluating PFS and OS. Moreover, pre-infusion SUVmax correlated with the severity of any subsequent CRS. We conclude that metabolic parameters measured using [18F]FDG PET/CT can identify DLBCL patients who will benefit most from CAR T-cell therapy, and the value before CAR T-cell infusion may predict its toxicity in advance.


Fluorodeoxyglucose F18 , Immunotherapy, Adoptive , Lymphoma, Large B-Cell, Diffuse , Positron Emission Tomography Computed Tomography , Humans , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Female , Middle Aged , Adult , Aged , Prognosis , Immunotherapy, Adoptive/adverse effects , Retrospective Studies , Young Adult , Receptors, Chimeric Antigen
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