Circulating miRNA-21 as early potential diagnostic biomarker for acute myocardial infarction: a meta-analysis.

Introduction: There exists a knowledge gap concerning the clinical significance of miRNA-21; therefore, in the present study, we aimed to estimate the diagnostic and prognostic accuracy and sensitivity of miRNA-21 in acute myocardial infarction (AMI) by performing an evidence-based meta-analysis of previous AMI-related clinical studies. Methods: Chinese and English literature published before April 2024 were searched, and data were reviewed and extracted. After quality appraisal, the STATA 16.0 software was used for the effect size analysis of the various treatments described in the literature. Results: A total of 14 valid documents were retrieved from 562 studies. The results of the systematic review revealed that for the patients with AMI vs. those without non-AMI, the aggregated odds ratio reached 5.37 (95% confidence interval 3.70-7.04). The general sensitivity and specificity for the circulating miRNA-21 levels in diagnosing AMI were 0.83 and 0.81, respectively. Discussion: Thus, the meta-analysis of 14 AMI-related clinical trials highlighted that miRNA-21 may serve as a promising biomarker for diagnosing AMI.

Depression exacerbates myocardial ischemia-reperfusion injury in mice via CNR2 gene and MIF-AMPK signaling pathway.

BACKGROUND: Myocardial ischemia-reperfusion(I/R)injury constitute the fundamental pathophysiology of acute myocardial infarction (AMI). Ischemic heart releases macrophage migration inhibitory factor (MIF), which activates MIF- AMPK signaling pathway. Depression is a significant risk factor for AMI. In a state of depression, peripheral expression of cannabinoid receptor 2 (CNR2) genes was downregulated. AIMS: We investigated the mechanism by which depression exacerbates myocardial I/R injury through the CNR2 and MIF-AMPK signaling pathways. METHODS: We established mouse models of depression and myocardial I/R. Left ventricular function was assessed using cardiac ultrasound and TTC staining. The protein levels of myocardial CNR2, MIF, AMPK, and ACC were determined by Western blot, while the expression level of CNR2 was measured using RT-qPCR. Additionally, MIF content in peripheral blood was quantified using ELISA. RESULTS: After I/R, the expression level of CNR2 was found to be lower in the depression group, leading to a deterioration in left heart function. Depressed mice exhibited lower secretion of MIF, accompanied by a decrease in the activation of the MIF-AMPK signaling pathway. However, injection of CNR2 agonist JWH133 prior to ischemia increased the activation of the MIF-AMPK signaling pathway, while CNR2 inhibitor AM630 decreased the activation. LIMITATIONS: Further research is needed to investigate the specific neuroendocrine mechanism affecting myocardial CNR2 expression in depression. And these experimental conclusions require further verification at the cellular level. CONCLUSIONS: The activation of CNR2 in myocardium following I/R is impeded by depression, thereby exacerbating myocardial I/R injury through attenuation of the MIF-AMPK signaling pathway activation.

Amphiphilic disodium glycyrrhizin as a co-former for ketoconazole co-amorphous systems: Biopharmaceutical properties and underlying molecular mechanisms.

Co-amorphous systems (CAMs) have been extensively investigated to improve the dissolution of hydrophobic drugs. However, drug precipitation during the storage or dissolution of CAMs has still been a major challenge. Here, disodium glycyrrhizin (Na2GA) was first used as a co-former in CAMs based on its multiple hydroxyl groups and amphiphilic structure. Ketoconazole (KTZ), a BCS class II drug, was selected as a model drug. KTZ-Na2GA CAMs at mass ratios of 1:1, 1:2.5, 1:5 and 1:10 were prepared by the spray drying method and further characterised by PXRD and DSC. The 1:2.5, 1:5 and 1:10 groups exhibited significantly enhanced Cmax (all approximately 26.67-fold) and stable maintenance of supersaturation compared to the crystalline KTZ and the corresponding physical mixtures in non-sink dissolution tests, while the 1:1 group exhibited an unstable medium Cmax (all approximately 14.67-fold). The permeability tests revealed that the permeation rate of KTZ in KTZ-Na2GA CAMs under the concentration of Na2GA in solution above the critical micelle concentration (CMC) showed a significant downwards trend compared to that below CMC. The underlying molecular mechanisms were involved in molecular miscibility, hydrogen bond interactions, solubilisation and crystallisation inhibition by Na2GA. Pharmacokinetic studies demonstrated that the AUC0-∞ of KTZ in 1:1, 1:2.5, 1:5 and 1:10 groups were significantly higher than those of the crystalline KTZ group with 2.13-, 2.30-, 2.16- and 1.86-fold, respectively (p < 0.01). In conclusion, Na2GA has proven to be a promising co-former in CAMs to enhance hydrophobic drug dissolution and bioavailability. Its effect on intestinal permeation rate of drugs also deserves attention.

Albumin-based co-loaded sonosensitizer and STING agonist nanodelivery system for enhanced sonodynamic and immune combination antitumor therapy.

STING agonists can activate natural and adaptive immune responses, and are expected to become a new type of immunotherapy drug for tumor therapy. However, how to target deliver STING agonists to tumor tissues is a key factor affecting the efficacy of tumor treatment. Sonodynamic therapy (SDT) has become a research hotspot in the field of cancer treatment due to its non-invasive, spatiotemporally controllable, and high tissue penetration capabilities. Therefore, how to choose the appropriate drug delivery strategy, build a suitable drug delivery system to co-deliver photosensitizers and STING agonists, is a challenge faced in the tumor treatment. In this study, we developed an albumin-based nanodelivery system named FA-ICG&MnOx@HSA that co-loaded the sonosensitizers indocyanine green (ICG) and manganese oxide (MnOx). This approach achieved folate receptor-targeting mediated tumor delivery and tumor microenvironment (TME)-responsive release facilitated by high levels of glutathione (GSH) and hydrogen peroxide (H2O2), which catalyze oxygen generation to potentiate SDT efficacy in killing tumors and inducing immunogenic cell death (ICD). Simultaneously, the released Mn2+ acted as a STING agonist promoting dendritic cell maturation, IFN-ß production, and proliferation of T cells. Ultimately, this albumin based co-loaded sonosensitizer and STING agonist demonstrated promising potential for advancing tumor treatment.

In Vivo Delivery Processes and Development Strategies of Lipid Nanoparticles.

Lipid nanoparticles (LNPs) represent an advanced and highly efficient delivery system for RNA molecules, demonstrating exceptional biocompatibility and remarkable delivery efficiency. This is evidenced by the clinical authorization of three LNP formulations: Patisiran, BNT162b2, and mRNA-1273. To further maximize the efficacy of RNA-based therapy, it is imperative to develop more potent LNP delivery systems that can effectively protect inherently unstable and negatively charged RNA molecules from degradation by nucleases, while facilitating their cellular uptake into target cells. Therefore, this review presents feasible strategies commonly employed for the development of efficient LNP delivery systems. The strategies encompass combinatorial chemistry for large-scale synthesis of ionizable lipids, rational design strategy of ionizable lipids, functional molecules-derived lipid molecules, the optimization of LNP formulations, and the adjustment of particle size and charge property of LNPs. Prior to introducing these developing strategies, in vivo delivery processes of LNPs, a crucial determinant influencing the clinical translation of LNP formulations, is described to better understand how to develop LNP delivery systems.

Immune checkpoint reprogramming via sequential nucleic acid delivery strategy optimizes systemic immune responses for gastrointestinal cancer immunotherapy.

Monoclonal antibodies targeting immune checkpoints have been widely applied in gastrointestinal cancer immunotherapy. However, systemic administration of various monoclonal antibodies does not often result in sustained effects in reversing the immunosuppressive tumor microenvironment (TME), which may be due to the spatiotemporal dynamic changes of immune checkpoints. Herein, we reported a novel immune checkpoint reprogramming strategy for gastrointestinal cancer immunotherapy. It was achieved by the sequential delivery of siPD-L1 (siRNA for programmed cell death ligand 1) and pOX40L (plasmid for OX40 ligand), which were complexed with two cationic polymer brush-grafted carbon nanotubes (dense short (DS) and dense long (DL)) designed based on the structural characteristics of nucleic acids and brush architectures. Upon administrating DL/pOX40L for the first three dosages, then followed by DS/siPD-L1 for the next three dosages to the TME, it upregulated the stimulatory checkpoint OX40L on dendritic cells (DCs) and downregulated inhibitory checkpoint PD-L1 on tumor cells and DCs in a sequential reprogramming manner. Compared with other combination treatments, this sequential strategy drastically boosted the DCs maturation, and CD8+ cytotoxic T lymphocytes infiltration in tumor site. Furthermore, it could augment the local antitumor response and improve the T cell infiltration in tumor-draining lymph nodes to reverse the peripheral immunosuppression. Our study demonstrated that sequential nucleic acid delivery strategy via personalized nanoplatforms effectively reversed the immunosuppression status in both tumor microenvironment and peripheral immune landscape, which significantly enhanced the systemic antitumor immune responses and established an optimal immunotherapy strategy against gastrointestinal cancer.

Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing.

Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal-organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.

Broadening Bandwidth in a Semi-Active Vibration Absorption System Utilizing Stacked Polyvinyl Chloride Gel Actuators.

Plasticized polyvinyl chloride (PVC) gel is a new soft and smart material, whose potential in electroactive variable stiffness can be used for vibration control in soft robotic systems. In this paper, a new semi-active vibration absorber is developed by stacking PVC gel actuator units. The absorption bandwidth of a single PVC gel absorber covers the range of three natural frequencies (76.5 Hz, 95 Hz, 124 Hz) of a rectangular steel plate in vibration attenuation. The maximum reduction percentage in acceleration amplitude is 63%. With stacked PVC gel actuator units, the absorption bandwidth can be shifted and obviously broadened.

Gender potentially affects early postoperative hyponatremia in pituitary adenoma: XGBoost-based predictive modeling.

Purpose: The occurrence of hyponatremia is a prevalent complication following transnasal transsphenoidal surgery for pituitary adenoma surgery, which adversely affects patient prognosis, hospitalization duration, and rehospitalization risk. The primary objective of this study is to strengthen the correlation between clinical factors associated with pituitary adenoma and postoperative hyponatremia. Additionally, the study aims to develop a predictive model for postoperative hyponatremia in patients with pituitary adenoma, with the ultimate goal of establishing a basis for reducing the occurrence of postoperative hyponatremia following surgical interventions. Methods: The chi-square test or Fisher test was employed for nominal data, while the t-test or Mann-Whitney test was utilized for continuous data analysis. In cases where the data exhibited statistical differences, binary logistic analysis was conducted to examine the risk and protective factors associated with postoperative hyponatremia. XGBoost was employed to construct predictive models for hyponatremia in this study. The patients were partitioned into training and test sets, and the most suitable parameters were determined through five-fold cross-validation and subsequently utilized for training on the training set. The discriminatory capability was assessed on the internal validation set. Results and conclusions: Out of the total 280 patients included in this investigation, 82 patients experienced early postoperative hyponatremia. Among these individuals, male gender (P = 0.02, odds ratio = 1.98) was identified as a risk factor for early postoperative hyponatremia, while preoperative chloride levels (P = 0.021, odds ratio = 0.866) and surgery time (P = 0.039, odds ratio = 0.990) were identified as protective factors against postoperative hyponatremia. The XGBoost model exhibited a sensitivity of 94.2%, a specificity of 61.5%, a positive predictive value of 51.6%, a negative predictive value of 96%, and identified male gender, preoperative sodium, and preoperative cortisol as the most significant predictors. Our findings indicate that gender may have influence in the development of early postoperative hyponatremia in patients with pituitary adenomas.

NIFK, a Potential Prognostic and Immunological Biomarker in Pan-- Cancer Analysis, Significantly Regulates Proliferation and Metastasis of Colorectal Cancer.

BACKGROUND: As a binding protein of Ki67, NIFK plays an important role in the mitosis of cells and is closely related to the progression of specific types of tumors. However, there is still a lack of systematic analysis of NIFK in pan-cancer and insufficient research to explore its role in human tumors. METHODS: We systematically evaluated the pan-cancer expression and mutation of NIFK in human cancers using data from The Cancer Genome Atlas (TCGA) through large-scale bioinformatics analysis. In addition, we explored the pan-cancer immunological characteristics of NIFK, especially in colorectal adenocarcinoma (COAD). Furthermore, we used single-cell sequencing to analyze the expression of NIFK in different cells of COAD tissues and performed GO, KEGG, and gene set enrichment analysis of NIFK in COAD. Lastly, we evaluated the effects of NIFK knockdown on the colorectal cancer cell lines in in vitro experiment. RESULTS: We found that NIFK was overexpressed in almost all types of tumors and showed significant prognostic efficacy. Additionally, correlations between NIFK and specific immune features, such as immune cell infiltration, immune checkpoint genes, TMB, and MSI, suggest that NIFK may be used to guide immunotherapy. Subsequently, it was found that the expression of NIFK was significantly upregulated in tumor cells through single-cell sequencing analysis, and the NIFK gene was closely associated with tumor progression and immune therapy response. Finally, we further elucidated the role of NIFK in colorectal cancer and found that downregulation of NIFK expression could inhibit the proliferation, migration, and invasion ability of colorectal cancer cells. CONCLUSION: The results of this study demonstrated that NIFK, as a member of the pan-cancer genes, will serve as a biomarker and a potential therapeutic target for a range of cancer types, providing new insight into precision medicine.

Systems genetics of influenza A virus-infected mice identifies TRIM21 as a critical regulator of pulmonary innate immune response.

Tripartite motif 21 (TRIM21) is a cytosolic Fc receptor that targets antibody-bound, internalized pathogens for destruction. Apart from this intrinsic defense role, TRIM21 is implicated in autoimmune diseases, inflammation, and autophagy. Whether TRIM21 participates in host interactions with influenza A virus (IAV), however, is unknown. By computational modeling of body weight and lung transcriptome data from the BXD parents (C57BL/6 J (B6) and DBA/2 J (D2)) and 41 BXD mouse strains challenged by IAV, we reveal that a Trim21-associated gene network modulates the early host responses to IAV infection. Trim21 transcripts were significantly upregulated in infected mice of both B6 and D2 backgrounds. Its expression was significantly higher in infected D2 than in infected B6 early after infection and significantly correlated with body weight loss. We identified significant trans-eQTL on chromosome 14 that regulates Trim21 expression. Nr1d2 and Il3ra were among the strongest candidate genes. Pathway analysis found Trim21 to be involved in inflammation and immunity related pathways, such as inflammation signaling pathways (TNF, IL-17, and NF-κB), viral detection signaling pathways (NOD-like and RIG-I-like), influenza, and other respiratory viral infections. Knockdown of TRIM21 in human lung epithelial A549 cells significantly augmented IAV-induced expression of IFNB1, IFNL1, CCL5, CXCL10, and IFN-stimulated genes including DDX58 and IFIH1, among others. Our data suggest that a TRIM21-associated gene network is involved in several aspects of inflammation and viral detection mechanisms during IAV infection. We identify and validate TRIM21 as a critical regulator of innate immune responses to IAV in human lung epithelial cells.

18 F-FDG PET/CT Versus 68 Ga-FAPI PET/CT in a Case of Isolated Nodal-Type Follicular Dendritic Cell Sarcoma.

ABSTRACT: Follicular dendritic cell sarcoma is a rare low-grade sarcoma originating from mesenchymal dendritic cells. We presented 18 F-FDG and 68 Ga-FAPI PET/CT findings in a 32-year-old woman with pathologically confirmed nodal-type follicular dendritic cell sarcoma. In this case, follicular dendritic cell sarcoma demonstrated lower uptake with FAPI than FDG.

177 Lu-DOTATATE in the Treatment of Recurrent Pheochromocytoma With Multiple Metastases.

ABSTRACT: The treatment of metastatic pheochromocytoma is challenging. We report a case of a woman with recurrent pheochromocytoma with multiple metastases who achieved excellent response after 4 cycles of 177 Lu-DOTATATE therapy. She did not experience any observable adverse effects. Her disease was still stable 6 months after the fourth cycle of treatment.

Photothermal Ferrotherapy - Induced Immunogenic Cell Death via Iron-Based Ternary Chalcogenide Nanoparticles Against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is highly malignant and prone to recurrence and metastasis. Patients with TNBC have limited therapeutic options, often resulting in poor prognosis. Some new treatments for TNBC have been considered in the past decade, such as immunotherapy, photothermal therapy (PTT), and ferroptosis therapy, that allow the rapid and minimally invasive ablation of cancer. However, a multifunctional nanodrug system with more potent efficacy for TNBC is still needed. The use of iron-based ternary chalcogenide nanoparticles (NPs), namely AgFeS2 , is reported, which synergistically combines photothermal therapy, ferrotherapy, and immunotherapy in one system for the treatment of TNBC. AgFeS2 possesses excellent photothermal conversion performance for tumor near-infrared (NIR) phototherapy. Upon photoirradiation, these NPs generate heat, accelerate the release of iron ions, and effectively catalyze the Fenton reaction, resulting in cell apoptosis and ferroptosis. Additionally, AgFeS2 promotes the release of tumor-specific antigens and triggers an immune response via immunogenic cell death (ICD), thereby providing unique synergistic mechanisms for cancer therapy. The present study demonstrates the great potential of iron-based ternary chalcogenide as a new therapeutic platform for a combination of photothermal therapy, ferrotherapy, and immunotherapy for the suppression of TNBC.

68 Ga-FAPI and 18 F-FDG PET/CT in Intravenous Leiomyomatosis.

ABSTRACT: Intravenous (IV) leiomyomatosis is a rare IV disease. Our case presents 68 Ga-FAPI and 18 F-FDG PET/CT findings of IV leiomyomatosis in a 37-year-old woman. Intravenous leiomyomatosis shows only mild FDG but intense 68 Ga-FAPI activity on PET/CT studies. In this case, 68 Ga-FAPI was superior to 18 F-FDG PET/CT in detecting IV leiomyomatosis.

Comparison of 18 F-FDG and 68 Ga-FAPI PET/CT in a Patient With Hepatic Perivascular Epithelioid Cell Neoplasm.

ABSTRACT: The prevalence of hepatic perivascular epithelioid cell neoplasm (PEComa) is extremely low, and imaging diagnosis is very difficult. We presented 18 F-FDG and 68 Ga-FAPI PET/CT findings in a 58-year-old woman with pathologically confirmed hepatic PEComa. The tumor showed intense 68 Ga-FAPI uptake but only mild 18 F-FDG activity on PET/CT studies. This case suggested that 68 Ga-FAPI PET/CT might be a useful tool for evaluation of hepatic PEComa with remarkable tumor-to-liver ratios.

Sequencing and analysis of micro RNAs in camel milk exosomes.

In order to study the species and functions of micro (mi)RNAs in the exosomes of camel milk, non-coding small (s)RNAs were sequenced and identified by Illumina sequencing technology, and the miRNA fraction was analysed by bioinformatics. After quality control, the average length of sRNA of camel milk exosomes was 18-24 nucleotides. A total of 2,659 miRNAs were identified, including 2,458 known, and 201 new miRNAs. Among the known miRNAs, miR-148a and let-7i had the highest expression levels. The results of gene ontology enrichment analysis indicated that the target genes of camel milk exosome miRNAs were involved in multicellular organismal, catabolic and other biological processes. They play role in the extracellular region, in the cytoskeleton and other cell components, in protein binding, but also have structural molecule activity and other molecular functions. According to the results of the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, the target genes of camel milk exosome miRNAs are involved in Alzheimer's disease, non-alcoholic fatty liver disease, Staphylococcus aureus infection and other pathological pathways. We speculate that the reported beneficial effect of camel milk in various pathologic conditions may be closely related to the regulatory function of the exosomal miRNAs exerted on target genes of the diseases.

The nucleus accumbens functional connectivity in patients with insomnia using resting-state fMRI.

Background: The aim of this study was to investigate the functional abnormalities between the nucleus accumbens (NAc) and the whole brain in individuals with Insomnia Disorder (ID) using resting-state functional magnetic resonance imaging (fMRI). Additionally, the study aimed to explore the underlying neural mechanisms of ID. Methods: We enrolled 18 participants with ID and 16 normal controls (NC). Resting-state functional connectivity (FC) between the NAc and the whole brain voxels was calculated and compared between the two groups to identify differential brain region. Receiver operating characteristic (ROC) curve analysis was employed to assess the ability of differential features to distinguish between groups. Furthermore, Pearson correlation analysis was performed to examine the relationship between neurocognitive scores and differential features. Results: The ID group exhibited significantly reduced FC values in several brain regions, including the right supplementary motor area, the bilateral middle frontal gyrus, the bilateral median cingulate and paracingulate gyri and the left precuneus. The area under the curve (AUC) of the classification model based on FC in these brain regions was 83.3%. Additionally, the abnormal functional changes observed in ID patients were positively correlated with the Fatigue Severity Scale (R = 0.650, p = 0.004). Conclusion: These findings suggest that the NAc may play a crucial role in the diagnosis of ID and could serve as a potential imaging biomarker, providing insights into the underlying neural mechanisms of the disorder.

Silk fibroin-gelatin photo-crosslinked 3D-bioprinted hydrogel with MOF-methylene blue nanoparticles for infected wound healing.

Photo-crosslinked hydrogel (PH) is an outstanding candidate for three-dimensional (3D) printing as a wound dressing because of its high efficiency in crosslinking and injectability. In this study, methylene blue (MB)-loaded UiO-66(Ce) nanoparticles (NPs) were synthesized to prevent drug self-aggregation and achieve the photodynamic therapy (PDT) effect for efficient antibacterial action. Then, a composite photocrosslinked silk fibroin (SF)/gelatin hydrogel loaded with MB@UiO-66(Ce) NPs (MB@UiO-66(Ce)/PH) was fabricated. The printability and the improvement of the mechanical properties of the hydrogel by the NPs were clarified. The hydrogel exhibited good biocompatibility and promoted the migration and proliferation of fibroblasts. With the PDT effect of MB@UiO-66(Ce) NPs, the hydrogel showed an excellent antibacterial effect, which became more pronounced as the concentration increased. In vivo study showed that the MB@UiO-66(Ce)/PH could fill the defects without gaps and accelerate the repair rate of full-thickness skin defects in mice. The MB@UiO-66(Ce)/PH with antibacterial properties and tissue healing-promoting ability provides a new strategy involving 3D bioprinting for preparing wound dressings.

Individual Proportion Loss of Functional Connectivity Strength: A Novel Individual Functional Connectivity Biomarker for Subjective Cognitive Decline Populations.

High individual variation in the subjective cognitive decline (SCD) population makes functional connectivity (FC) biomarkers unstable. This study proposed a novel individual FC index, named individual proportion loss of functional connectivity strength (IPLFCS), and explored potential biomarkers for SCD using this new index. We proposed an IPLFCS analysis framework and compared it with traditional FC in Chinese and Western cohorts. Post hoc tests were used to determine biomarkers. Pearson's correlation analysis was used to investigate the correlation between neuropsychological scores or cortical amyloid deposits and IPLFCS biomarkers. Receiver operating characteristic curves were utilized to evaluate the ability of potential biomarkers to distinguish between groups. IPLFCS of the left middle temporal gyrus (LMTG) was identified as a potential biomarker. The IPLFC was correlated with the traditional FC (r = 0.956, p < 0.001; r = 0.946, p < 0.001) and cortical amyloid deposition (r = -0.245, p = 0.029; r = -0.185, p = 0.048) in both cohorts. Furthermore, the IPLFCS decreased across the Alzheimer's disease (AD) continuum. Its diagnostic efficiency was superior to that of existing fMRI biomarkers. These findings suggest that IPLFCS of the LMTG could be a potential biomarker of SCD.