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JOURNAL/nrgr/04.03/01300535-202504000-00028/figure1/v/2024-07-06T104127Z/r/image-tiff The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration. However, it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains. This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals. Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin. Recently, we showed that the PINK1 kinase is selectively expressed as a truncated form (PINK1-55) in the primate brain. In the present study, we used multiple antibodies, including our recently developed monoclonal anti-PINK1, to validate the selective expression of PINK1 in the primate brain. We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages, which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains. PINK1 was enriched in the membrane-bound fractionations, whereas Parkin was soluble with a distinguishable distribution. Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes, though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress. These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

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Background: Previous studies based on resting-state functional magnetic resonance imaging(rs-fMRI) and voxel-based morphometry (VBM) have demonstrated significant abnormalities in brain structure and resting-state functional brain activity in patients with early-onset schizophrenia (EOS), compared with healthy controls (HCs), and these alterations were closely related to the pathogenesis of EOS. However, previous studies suffer from the limitations of small sample sizes and high heterogeneity of results. Therefore, the present study aimed to effectively integrate previous studies to identify common and specific brain functional and structural abnormalities in patients with EOS. Methods: The PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases were systematically searched to identify publications on abnormalities in resting-state regional functional brain activity and gray matter volume (GMV) in patients with EOS. Then, we utilized the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software to conduct a whole-brain voxel meta-analysis of VBM and rs-fMRI studies, respectively, and followed by multimodal overlapping on this basis to comprehensively identify brain structural and functional abnormalities in patients with EOS. Results: A total of 27 original studies (28 datasets) were included in the present meta-analysis, including 12 studies (13 datasets) related to resting-state functional brain activity (496 EOS patients, 395 HCs) and 15 studies (15 datasets) related to GMV (458 EOS patients, 531 HCs). Overall, in the functional meta-analysis, patients with EOS showed significantly increased resting-state functional brain activity in the left middle frontal gyrus (extending to the triangular part of the left inferior frontal gyrus) and the right caudate nucleus. On the other hand, in the structural meta-analysis, patients with EOS showed significantly decreased GMV in the right superior temporal gyrus (extending to the right rolandic operculum), the right middle temporal gyrus, and the temporal pole (superior temporal gyrus). Conclusion: This meta-analysis revealed that some regions in the EOS exhibited significant structural or functional abnormalities, such as the temporal gyri, prefrontal cortex, and striatum. These findings may help deepen our understanding of the underlying pathophysiological mechanisms of EOS and provide potential biomarkers for the diagnosis or treatment of EOS.

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Sugammadex (SUG) is a novel antagonist of neuromuscular blocking agents (NMBAs). The NMBA rocuronium is usually employed to obtain better surgical conditions in kidney transplant. Nevertheless, rocuronium has several disadvantages, such as an increased risk of pulmonary complications. Thus, SUG is vital to kidney-transplant surgery. However, because SUG is excreted by the kidneys in prototypes, the pharmacokinetics (PK) may be affected in patients with renal impairment. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to monitor SUG in plasma samples to investigate the PK of SUG in kidney-transplant patients. Due to the complexity and limitation of other methods of sample preparation, magnetic solid-phase extraction (MSPE) was adopted to purify samples. Chromatographic separation was obtained using a reversed-phase Polaris® C18 column and gradient elution with 0.1% formic acid (FA) in water as phase A and in methanol (MeOH) as phase B as mobile phases. The transitions 999.7 → 963.9 (m/z) and 1055.7 → 1012.2 (m/z) were used to quantify SUG and ORG26265, respectively, under negative electrospray ionization. A linear calibration curve was achieved in concentrations varying from 100 to 10 000 ng mL-1. The acceptable accuracy varied from 95.7% to 106.4%, and intra- and inter-precision did not exceed 15% (20% at the lower limit of quantitation (LLOQ)). The matrix effect, stability, dilution integrity, and carry-over were validated. This method was applied successfully for the PK study of 13 recipients and 12 donors of kidney transplant after intravenous injection of SUG (2 mL per kg bodyweight).

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The fundamental pathophysiological mechanism in the progression of chronic heart failure following acute myocardial infarction (AMI) is ventricular remodeling, in which innate and adaptive immunity both play critical roles. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to function in a range of pathological conditions, such as infections, inflammation, autoimmune diseases, and tumors. However, it is unclear how MDSCs contribute to cardiac remodeling following AMI. This study aimed to identify the function and underlying mechanism of MDSCs in controlling cardiac remodeling following AMI. Following AMI in mice, MDSCs frequencies changed dynamically, considerably increased on day 7 in blood, spleens, lymph nodes and hearts, and decreased afterwards. Consistently, mice with AMI displayed enhanced cardiac function on day 14 post-AMI, reduced infract size and higher survival rates on day 28 post-AMI following the adoptive transfer of MDSCs. Furthermore, MDSCs inhibited the inflammatory response by decreasing pro-inflammatory cytokine (TNF-α, IL-17, Cxcl-1, and Cxcl-2) expression, up-regulating anti-inflammatory cytokine (TGF-ß1, IL-10, IL-4, and IL-13) expression, reducing CD3+ T cell infiltration in the infarcted heart and enhancing M2 macrophage polarization. Mechanistically, MDSCs improved the release of anti-inflammatory factors (TGF-ß1 and IL-10) and decreased the injury of LPS-induced cardiomyocytes in vitro in a manner dependent on cell-cell contact. Importantly, blockade of IL-10 partially abolished the cardioprotective role of MDSCs. This study found that MDSCs contributed to the restoration of cardiac function and alleviation of adverse cardiac remodeling after AMI possibly by inhibiting inflammation.

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BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by an excessive host response to infection, manifested by elevated levels of inflammatory cytokines. At present, the use of hemoperfusion to remove inflammatory cytokines from the bloodstream has been expanding. Meanwhile, the pharmacokinetics and pharmacodynamics characteristics of antibiotics in critically ill patients may be impacted by hemoperfusion. CASE PRESENTATION: The patient was a 69-year-old male with poorly controlled type 2 diabetes. When admitted to the ICU, Multiple Organ Dysfunction Syndrome (MODS) appeared within 48 h, and he was suspected of septic shock due to acute granulocytopenia and significantly increased procalcitonin. Broad-spectrum antibiotics imipenem was administered according to Sepsis 3.0 bundle and hemoperfusion lasting 4 h with a neutron-macroporous resin device (HA-380, Jafron, China) five times was conducted to lower the extremely high value of serum inflammatory factors. Blood samples were collected to measure imipenem plasma concentration to investigate the effect of hemoperfusion quantitatively. This study showed that 4 h of hemoperfusion had a good adsorption ability on inflammatory factors and could remove about 75.2% of imipenem. CONCLUSIONS: This case demonstrated the high adsorption capacity of hemoperfusion on imipenem in critically ill patients. It implies a timely imipenem supplement is required, especially before hemoperfusion.

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In recent years, EEG-based emotion recognition technology has made progress, but there are still problems of low model efficiency and loss of emotional information, and there is still room for improvement in recognition accuracy. To fully utilize EEG's emotional information and improve recognition accuracy while reducing computational costs, this paper proposes a Convolutional-Recurrent Hybrid Network with a dual-stream adaptive approach and an attention mechanism (CSA-SA-CRTNN). Firstly, the model utilizes a CSAM module to assign corresponding weights to EEG channels. Then, an adaptive dual-stream convolutional-recurrent network (SA-CRNN and MHSA-CRNN) is applied to extract local spatial-temporal features. After that, the extracted local features are concatenated and fed into a temporal convolutional network with a multi-head self-attention mechanism (MHSA-TCN) to capture global information. Finally, the extracted EEG information is used for emotion classification. We conducted binary and ternary classification experiments on the DEAP dataset, achieving 99.26% and 99.15% accuracy for arousal and valence in binary classification and 97.69% and 98.05% in ternary classification, and on the SEED dataset, we achieved an accuracy of 98.63%, surpassing relevant algorithms. Additionally, the model's efficiency is significantly higher than other models, achieving better accuracy with lower resource consumption.

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BACKGROUND: Aerobic glycolysis and the cell cycle are well-established tumor hallmarks. Understanding their relationship could help to unravel the pathogenic mechanisms of breast cancer (BC) and suggest potential new strategies for treatment. METHODS: Glycolysis-related genes (GRGs) were downloaded from the Reactome database and screened using univariate Cox analysis. The consensus clustering method was employed to identify a glycolytic activity signature (GAS) using the Gene Expression Omnibus (GEO) dataset. A nomogram risk prediction model was constructed using coefficients from univariate Cox analysis. Immune cell infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm. Gene co-expression modules were created using weighted correlation network analysis (WGCNA) to identify hub genes. Gene expression in three BC cell lines was quantified using Quantitative Reverse Transcriptase Polymera (qRT-PCR). Single-cell RNA sequencing (scRNA-seq) data was used to examine the relationship between GAS and hub genes. The sensitivity of different groups to cell cycle-related clinical drugs was also examined. RESULTS: BC with high GAS (HGAS) showed high tumor grade and recurrence rate. HGAS was a prognostic indicator of worse overall survival (OS) in BC patients. HGAS BC showed more abundant immune cells and significantly higher expression of immunomodulators compared to BC with low GAS (LGAS). HGAS BC also showed enhanced cell cycle pathway, with high mRNA and protein expression levels of Cyclin B2 (CCNB2), a key component of the cell cycle pathway. Importantly, scRNA-seq analysis revealed that elevated CCNB2 expression was positively correlated with HGAS in triple-negative BC (TNBC). This was validated in clinical samples from TNBC patients. High expression of CCNB2 was found in three BC cell lines, and was also an indicator of poor prognosis. HGAS BC showed high sensitivity to several cell cycle-related clinical drugs, with 9 of these also showing activity in BC with high CCNB2 expression. CONCLUSIONS: HGAS was associated with enhanced cell cycle pathway and immune activity in BC. These results suggest that CCNB2 is a potential key therapeutic target in BC patients.

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Non-healing diabetic wounds and ulcer complications, with persistent cell dysfunction and obstructed cellular processes, are leading causes of disability and death in patients with diabetes. Currently, there is a lack of guideline-recommended hypoglycemic drugs in clinical practice, likely due to limited research and unclear mechanisms. In this study, it is demonstrated that liraglutide significantly accelerates wound closure in diabetic mouse models (db/db mice and streptozotocin-induced mice) by improving re-epithelialization, collagen deposition, and extracellular matrix remodeling, and enhancing the proliferation, migration, and adhesion functions of keratinocytes. However, these effects of improved healing by liraglutide are abrogated in dedicator of cytokinesis 5 (Dock5) keratinocyte-specific knockout mice. Mechanistically, liraglutide induces cellular function through stabilization of unconventional myosin 1c (Myo1c). Liraglutide directly binds to Myo1c at arginine 93, enhancing the Myo1c/Dock5 interaction by targeting Dock5 promoter and thus promoting the proliferation, migration, and adhesion of keratinocytes. Therefore, this study provides insights into liraglutide biology and suggests it may be an effective treatment for diabetic patients with wound-healing pathologies.

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Although Digital Subtraction Angiography (DSA) is the most important imaging for visualizing cerebrovascular anatomy, its interpretation by clinicians remains difficult. This is particularly true when treating arteriovenous malformations (AVMs), where entangled vasculature connecting arteries and veins needs to be carefully identified. The presented method aims to enhance DSA image series by highlighting critical information via automatic classification of vessels using a combination of two learning models: An unsupervised machine learning method based on Independent Component Analysis that decomposes the phases of flow and a convolutional neural network that automatically delineates the vessels in image space. The proposed method was tested on clinical DSA images series and demonstrated efficient differentiation between arteries and veins that provides a viable solution to enhance visualizations for clinical use.

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PURPOSE: A growing body of evidence has elucidated that the gut microbiota has a crucial impact on the pathophysiological process of atopic diseases. Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is a local atopic disease of the systemic immune response. Alterations in the gut microbiome in eCRSwNP patients remain largely undefined. METHODS: 16S rRNA gene sequencing was performed in a cross-sectional study of 17 eCRSwNP patients, 9 noneCRSwNP patients and 13 healthy controls, and gut microbiota DNA sequencing between each pair of groups was compared using bioinformatic methods. RESULTS: Compared with that of healthy controls, the gut microbiomes of eCRSwNP patients were characterised by a distinct overall microbial composition. However, no significant differences were found in the alpha diversity of the gut microbiota between patients and healthy controls. The distinct differences in microbial composition were significantly correlated with the severity of disease. At the genus level, the abundance of Faecalibacterium positively correlated with Lund-Mackay CT scores. Similarly, the abundance of Turicibacter positively correlated with the percentage of tissue eosinophils. CONCLUSIONS: We found alterations in the gut microbiome in eCRSwNP patients, and the alterations in the gut microbiome were correlated with the severity of disease.

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BACKGROUND: Poor reporting quality and spin in randomized controlled trial (RCT) abstracts can lead to misinterpretation and distorted interpretation of results. OBJECTIVES: This methodological study aimed to assess the reporting quality and spin among RCT abstracts on splint therapy for temporomandibular disorders (TMD) and explore the association between spin and potentially related factors. METHODS: The authors searched PubMed for RCTs on splint therapy for TMD. The reporting quality of each abstract was assessed using the original 16-item CONSORT for abstracts checklist. The authors evaluated the presence and characteristics of spin only in abstracts with nonsignificant primary outcomes according to pre-determined spin strategies. Logistic regression analyses were performed to identify factors associated with the presence of spin. RESULTS: A total of 148 abstracts were included in the reporting quality evaluation. The mean overall CONSORT score (OCS) was 5.86 (score range: 0-16). Only interventions, objectives and conclusions were adequately reported. Of the 61 RCT abstracts included for spin analysis, spin was identified in 38 abstracts (62.3%), among which 32 abstracts (52.3%) had spin in the Results section and 21 (34.4%) had spin in the Conclusions section. A significantly lower presence of spin was found in studies with exact p-value reporting (OR: 0.170; 95% CI: 0.032-0.887; p = .036) and a two-arm comparison design (OR: 11.777; 95% CI: 2.171-63.877; p = .004). CONCLUSIONS: The reporting quality of RCT abstracts on splint therapy for TMD is suboptimal and the prevalence of spin is high. More awareness and joint efforts are needed to improve reporting quality and minimize spin.

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Aiming at the problem that existing emotion recognition methods fail to make full use of the information in the time, frequency, and spatial domains in the EEG signals, which leads to the low accuracy of EEG emotion classification, this paper proposes a multi-feature, multi-frequency band-based cross-scale attention convolutional model (CATM). The model is mainly composed of a cross-scale attention module, a frequency-space attention module, a feature transition module, a temporal feature extraction module, and a depth classification module. First, the cross-scale attentional convolution module extracts spatial features at different scales for the preprocessed EEG signals; then, the frequency-space attention module assigns higher weights to important channels and spatial locations; next, the temporal feature extraction module extracts temporal features of the EEG signals; and, finally, the depth classification module categorizes the EEG signals into emotions. We evaluated the proposed method on the DEAP dataset with accuracies of 99.70% and 99.74% in the valence and arousal binary classification experiments, respectively; the accuracy in the valence-arousal four-classification experiment was 97.27%. In addition, considering the application of fewer channels, we also conducted 5-channel experiments, and the binary classification accuracies of valence and arousal were 97.96% and 98.11%, respectively. The valence-arousal four-classification accuracy was 92.86%. The experimental results show that the method proposed in this paper exhibits better results compared to other recent methods, and also achieves better results in few-channel experiments.

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OBJECTIVES: This study aimed to provide visualized knowledge maps to show the evolving trends and key focal points of Class III malocclusion research through a comprehensive bibliometric analysis. MATERIALS AND METHODS: Class III malocclusion research published between 2000 and 2023 was retrieved from the Web of Science Core Collection. VOSviewer was utilized to count the citation and publication number of authors, institutions, countries and journals. Co-occurrence, co-citation, and cluster analyses and burst detection were conducted using CiteSpace. RESULTS: A total of 3,682 publications on Class III malocclusion were included in the bibliometric analysis. During 2000-2023, both the annual publication count and citation frequency exhibited a gradual upward trajectory, with a noticeable surge in recent years. In terms of production and citation counts of Class III malocclusion research, the core journal is the American Journal of Orthodontics and Dentofacial Orthopedics. Furthermore, apart from the primary keyword 'Class III malocclusion', 'orthognathic surgery' was identified as keyword with the most frequency. The cluster analysis of cited references reveals that the research focal points have shifted to 'skeletal anchorage' and 'surgery-first approach'. Furthermore, the burst detection identified 'quality of life' as a potential research hotspot since it has recently gained increasing scholarly attention. CONCLUSIONS: The current study provides scholars with the knowledge maps of evolving trends and prominent topics of Class III malocclusion research and a summary of research progress on various priorities during different periods. These findings are expected to provide a valuable guidance to facilitate the future research on Class III malocclusion.

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Because of the pathological indication and the physiological functions, bile acids (BAs) have occupied the research hotspot in recent decades. Although extensive efforts have been paid onto BAs sub-metabolome characterization, as the subfamily, BA glucuronides (gluA-BAs) profile is seldom concerned. Here, we made efforts to develop a LC-MS/MS program enabling quantitative gluA-BAs sub-metabolome characterization and to explore the differential species in serum between intrahepatic cholestasis of pregnancy (ICP) patients and healthy subjects. To gain as many authentic gluA-BAs as possible, liver microsomes from humans, rats, and mice were deployed to conjugate glucuronyl group to authentic BAs through in vitro incubation. Eighty gluA-BAs were captured and subsequently served as authentic compounds to correlate MS/MS spectral behaviors to structural features using squared energy-resolved MS program. Optimal collision energy (OCE) of [M-H]->[M-H-176.1]- was jointly administrated by [M-H]- mass and glucuronidation site, and identical exciting energies corresponding to 50% survival rate of 1st-generation fragment ion (EE50) were observed merely when the aglycone of a gluA-BA was consistent with the suspected structure. Through integrating high-resolution m/z, OCE, and EE50 information to identify gluA-BAs in a BAs pool, 97 ones were found and identified, and further, quantitative program was built for all annotated gluA-BAs by assigning OCEs to [M-H]->[M-H-176.1]- ion transitions. Quantitative gluA-BAs sub-metabolome of ICP was different from that of the healthy group. More GCDCA-3-G, GDCA-3-G, TCDCA-7-G, TDCA-3-G, and T-ß-MCA-3-G were distributed in the ICP group. Above all, this study not only offered a promising analytical tool for in-depth gluA-BAs sub-metabolome characterization, but also clarified gluA-BAs allowing the differentiation of ICP and healthy subjects.

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Objectives: Patients with type 1 diabetes (T1D) face unique challenges in glycaemic control due to the complexity and uniqueness of the dietary structure in China, especially in terms of postprandial glycaemic response (PPGR). This study aimed to establish a personalized model for predicting PPGR in patients with T1D. Materials and methods: Data provided by the First People's Hospital of Yunnan Province, 13 patients with T1D, were recruited and provided with an intervention for at least two weeks. All patients were asked to wear a continuous glucose monitoring (CGM) device under free-living conditions during the study period. To tackle the challenge of incomplete data from wearable devices for CGM measurements, the GAIN method was used in this paper to achieve a more rational interpolation process. In this study, patients' PPGRs were calculated, and a LightGBM prediction model was constructed based on a Bayesian hyperparameter optimisation algorithm and a random search algorithm, which integrated glucose measurement, insulin dose, dietary nutrient content, blood measurement and anthropometry as inputs. Results: The experimental outcomes revealed that the PPGR prediction model presented in this paper demonstrated superior accuracy (R=0.63) compared to both the carbohydrate content only model (R=0.14) and the baseline model emulating the standard of care for insulin administration (R=0.43). In addition, the interpretation of the model using the SHAP method showed that blood glucose levels at meals and blood glucose trends 30 minutes before meals were the most important features of the model. Conclusion: The proposed model offers a heightened precision in predicting PPGR in patients with T1D, so it can better guide the diet plan and insulin intake dose of patients with T1D.

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The investigation of lunar soil encompasses extensive periods, employs many improvement methods, and has generated several simulants. The improvement of lunar soil has recently garnered growing interest as an aspect of In-Situ Resource Utilization (ISRU) for regolith. It is crucial to clarify the challenges of utilizing lunar soil as a planting substrate to develop more effective techniques. This review presents a comprehensive analysis of research on improving lunar soil properties, highlights the disparities in mineral composition between real lunar soil (also called regolith) and simulated lunar soil, then details their deficiencies as planting substrates. Following an investigation of existing improvement methods, a dilemma of metals、salt precipitation and high pH caused by adding organic matter alone was noted, while the function of microbes (bacteria, algae, and lichens) in improvement processes was assessed. Finally, we present a perspective on future the lunar soil plantable research development based on the Bioregenerative Life Support System (BLSS). This review aims to promote the engineering application of lunar soil improvements and sustainable development. We hope that one day, regolith will enable plants to flourish on the Moon.

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Glucagon receptor (GCGR) agonism offers potentially greater effects on the mitigation of hepatic steatosis. However, its underlying mechanism is not fully understood. Here, it screened tetraspanin CD9 might medicate hepatic effects of GCGR agonist. CD9 is decreased in the fatty livers of patients and upregulated upon GCGR activation. Deficiency of CD9 in the liver exacerbated diet-induced hepatic steatosis via complement factor D (CFD) regulated fatty acid metabolism. Specifically, CD9 modulated hepatic fatty acid synthesis and oxidation genes through regulating CFD expression via the ubiquitination-proteasomal degradation of FLI1. In addition, CD9 influenced body weight by modulating lipogenesis and thermogenesis of adipose tissue through CFD. Moreover, CD9 reinforcement in the liver alleviated hepatic steatosis, and blockage of CD9 abolished the remission of hepatic steatosis induced by cotadutide treatment. Thus, CD9 medicates the hepatic beneficial effects of GCGR signaling, and may server as a promising therapeutic target for hepatic steatosis.

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Purpose: This study aimed to investigate the relationship between temporomandibular joint (TMJ) effusion and TMJ pain, as well as jaw function limitation in patients via two-dimensional (2D) and three-dimensional (3D) magnetic resonance imaging (MRI) evaluation. Patients and Methods: 121 patients diagnosed with temporomandibular disorder (TMD) were included. TMJ effusion was assessed qualitatively using MRI and quantified with 3D Slicer software, then graded accordingly. In addition, a visual analogue scale (VAS) was employed for pain reporting and an 8-item Jaw Functional Limitations Scale (JFLS-8) was utilized to evaluate jaw function limitation. Statistical analyses were performed appropriately for group comparisons and association determination. A probability of p<0.05 was considered statistically significant. Results: 2D qualitative and 3D quantitative strategies were in high agreement for TMJ effusion grades (κ = 0.766). No significant associations were found between joint effusion and TMJ pain, nor with disc displacement and JLFS-8 scores. Moreover, the binary logistic regression analysis showed significant association between sex and the presence of TMJ effusion, exhibiting an Odds Ratio of 5.168 for females (p = 0.008). Conclusion: 2D qualitative evaluation was as effective as 3D quantitative assessment for TMJ effusion diagnosis. No significant associations were found between TMJ effusion and TMJ pain, disc displacement or jaw function limitation. However, it was suggested that female patients suffering from TMD may be at a risk for TMJ effusion. Further prospective research is needed for validation.