Serum apelin as a potential biomarker for infantile hemangiomas.

BACKGROUND: Infantile hemangiomas (IHs) are common benign vascular tumors in infants. Apelin, an endogenous cytokine, is implicated in the angiogenesis of neoplastic diseases. We aimed to explore the association between apelin and IHs, providing a foundation for clinical applications. METHODS: We identified differential expression of apelin in proliferative IHs compared to healthy controls (HCs) through bioinformatics analysis of publicly available databases and verified by Immunofluorescence. Enzyme-linked immunosorbent assay was used to quantify the serum levels of apelin and vascular endothelial growth factor (VEGF) in a cohort of 116 cases of proliferative IHs, 65 cases of capillary malformations (CMs), and 70 HCs. RESULTS: Apelin and APJ (APLNR, apelin receptor) were identified as the significantly upregulated differentially expressed genes (DEGs) in proliferative IHs. Immunofluorescence staining indicated high expression of apelin in proliferative IHs, while minimal expression in non-IH lesions. Apelin in IHs was reduced following 6 months of propranolol treatment. Serum apelin levels were significantly higher in the IH group compared to both the CM and HC groups. Moreover, apelin exhibited excellent discriminatory ability in distinguishing IHs from HCs, with an area under the curve (AUC) exceeding 0.90. A positive correlation was observed between the levels of apelin and the size of superficial IHs. The expression profiles of VEGF and apelin in IHs were found to be consistent. CONCLUSIONS: Apelin shows promise as a potential biomarker for IHs. The association between apelin and IH size, as well as its responsiveness to propranolol treatment, indicates its possible utility as a valuable indicator for the therapeutic evaluation of IHs.

Mining key circRNA-associated-ceRNA networks for milk fat metabolism in cows with varying milk fat percentages.

BACKGROUND: Cow milk fat is an essential indicator for evaluating and measuring milk quality and cow performance. Growing research has identified the molecular functions of circular RNAs (circRNAs) necessary for mammary gland development and lactation in mammals. METHOD: The present study analyzed circRNA expression profiling data in mammary epithelial cells (MECs) from cows with highly variable milk fat percentage (MFP) using differential expression analysis and weighted gene co-expression network analysis (WGCNA). RESULTS: A total of 309 differentially expressed circRNAs (DE-circRNAs) were identified in the high and low MFP groups. WGCNA analysis revealed that the pink module was significantly associated with MFP (r = - 0.85, P = 0.007). Parental genes of circRNAs in this module were enriched mainly in lipid metabolism-related signaling pathways, such as focal adhesion, ECM-receptor interaction, adherens junction and AMPK. Finally, six DE-circRNAs were screened from the pink module: circ_0010571, circ_0007797, circ_0002746, circ_0003052, circ_0004319, and circ_0012840. Among them, circ_0002746, circ_0003052, circ_0004319, and circ_0012840 had circular structures and were highly expressed in mammary tissues. Subcellular localization revealed that these four DE-circRNAs may play a regulatory role in the mammary glands of dairy cows, mainly as competitive endogenous RNAs (ceRNAs). Seven hub target genes (GNB1, GNG2, PLCB1, PLCG1, ATP6V0C, NDUFS4, and PIGH) were obtained by constructing the regulatory network of their ceRNAs and then analyzed by CytoHubba and MCODE plugins in Cytoscape. Functional enrichment analysis revealed that these genes are crucial and most probable ceRNA regulators in milk fat metabolism. CONCLUSIONS: Our study identified several vital circRNAs and ceRNAs affecting milk fat synthesis, providing new research ideas and a theoretical basis for cow lactation, milk quality, and breed improvement.

Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6.

BACKGROUND: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. OBJECTIVE: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. METHODS: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. RESULTS: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-ß signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. CONCLUSION: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

New insights into the role of macrophages in cancer immunotherapy.

Macrophages are the main component of the tumor microenvironment, which are differentiated from monocytes in the blood and play an important role in cancer development. Tumor-associated macrophages (TAMs) can promote tumor growth, invasion, metastasis, and resistance to anti-programmed death receptor 1 therapy by regulating programmed cell death ligand 1 expression and interacting with other immune cells in the tumor microenvironment. However, when activated properly, macrophages can also play an anti-tumor role by enhancing the phagocytosis and cytotoxicity of tumor cells. TAM is associated with poor prognosis and drug resistance in patients treated with immunotherapy, indicating that macrophages are attractive targets for combined therapy in cancer treatment. Combination of targeting TAMs and immunotherapy overcomes the drug resistance and achieved excellent results in some cancers, which may be a promising strategy for cancer treatment in the future. Herein, we review the recent findings on the role of macrophages in tumor development, metastasis, and immunotherapy. We focus mainly on macrophage≥centered therapy, including strategies to deplete and reprogram TAMs, which represent the potential targets for improving tumor immunotherapy efficacy.

Multi-layer CNN-LSTM network with self-attention mechanism for robust estimation of nonlinear uncertain systems.

Introduction: With the help of robot technology, intelligent rehabilitation of patients with lower limb motor dysfunction caused by stroke can be realized. A key factor constraining the clinical application of rehabilitation robots is how to realize pattern recognition of human movement intentions by using the surface electromyography (sEMG) sensors to ensure unhindered human-robot interaction. Methods: A multilayer CNN-LSTM prediction network incorporating the self-attention mechanism (SAM) is proposed, in this paper, which can extract and learn the periodic and trend characteristics of the sEMG signals, and realize the accurate autoregressive prediction of the human motion information. Firstly, the multilayer CNN-LSTM network utilizes the CNN layer for initial feature extraction of data, and the LSTM network is used to improve the enhancement of the historical time-series features. Then, the SAM is used to improve the global feature extraction performance and parallel computation speed of the network. Results: In comparison with existing test is carried out using actual data from five healthy subjects as well as a clinical hemiplegic patient to verify the superiority and practicality of the proposed algorithm. The results show that most of the model's prediction R > 0.9 for different motion states of healthy subjects; in the experiments oriented to the motion characteristics of patient subjects, the angle prediction results of R > 0.99 for the untrained data on the affected side, which proves that our proposed model also has a better effect on the angle prediction of the affected side. Discussion: The main contribution of this paper is to realize continuous motion estimation of ankle joint for healthy and hemiplegic individuals under non-ideal conditions (weak sEMG signals, muscle fatigue, high muscle tension, etc.), which improves the pattern recognition accuracy and robustness of the sEMG sensor-based system.

Enhancing Efficiency and High-Value Chemicals Generation through Coupling Photocatalytic CO2 Reduction with Propane Oxidation.

Conversion of CO2 into high-value chemicals using solar energy is one of promising approaches to achieve carbon neutrality. However, the oxidation of water in the photocatalytic CO2 reduction is kinetically unfavorable due to multi-electron and proton transfer processes, along with the difficulty in generating O-O bonds. To tackle these challenges, this study investigated the coupling reaction of photocatalytic CO2 reduction and selective propane oxidation using the Pd/P25 (1 wt%) catalyst. Our findings reveal a significant improvement in CO2 reduction, nearly fivefold higher, achieved by substituting water oxidation with selective propane oxidation. This substitution not only accelerates the process of CO2 reduction but also yields valuable propylene. The relative ease of propane oxidation, compared to water, appears to increase the density of photogenerated electrons, ultimately enhancing the efficiency of CO2 reduction. We further found that hydroxyl radicals and reduced intermediate (carboxylate species) played important roles in the photocatalytic reaction. These findings not only propose a potential approach for the efficient utilization of CO2 through the coupling of selective propane oxidation into propylene, but also provide insights into the mechanistic understanding of the coupling reaction.

Identification of key differentially methylated genes in regulating muscle development and intramuscular fat deposition in chickens.

Muscle development and intramuscular fat (IMF) deposition are intricate physiological processes characterized by multiple gene expressions and interactions. In this research, the phenotypic variations in the breast muscle of Jingyuan chickens were examined at three different time points: 42, 126, and 180 days old. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify differentially methylated genes (DMGs) responsible for regulating muscle development and IMF deposition. The findings indicate a significant increase in breast muscle weight (BMW), myofiber diameter, and cross-sectional area, as well as IMF content, in correlation with the progressive number of growing days in Jingyuan chickens. The findings also revealed that 380 hypo-methylated and 253 hyper-methylated DMGs were identified between the three groups of breast muscle. Module gene and DMG association analysis identified m6A methylation-mediated multiple DMGs associated with muscle development and fat metabolism. In vitro cell modeling analysis reveals stage-specific differences in the expression of CUBN, MEGF10, BOP1, and BMPR2 during the differentiation of myoblasts and intramuscular preadipocytes. Cycloleucine treatment significantly inhibited the expression levels of CUBN, BOP1, and BMPR2, and promoted the expression of MEGF10. These results suggest that m6A methylation-mediated CUBN, MEGF10, BOP1, and BMPR2 can serve as potential candidate genes for regulating muscle development and IMF deposition, and provide an important theoretical basis for further investigation of the functional mechanism of m6A modification involved in adipogenesis.

Structure-based approaches for the design of 6-aryl-1-(3,4,5-trimethoxyphenyl)-1H-benzo[d][1,2,3]triazoles as tubulin polymerization inhibitors.

The colchicine binding site on tubulin has been widely acknowledged as an attractive target for anticancer drug exploitation. Here, we reported the structural optimization of the lead compound 4, which was proved in our previous work as a colchicine binding site inhibitor (CBSI). Based on docking researches for the active binding conformation of compound 4, a series of novel 6-aryl-1-(3,4,5-trimethoxyphenyl)-1H-benzo[d][1,2,3]triazole derivatives (9a-9x) were developed by replacing a CH group in the 1H-benzo[d]imidazole skeleton of compound 4 with a nitrogen atom as a hydrogen bond acceptor. Among them, compound 9a showed the strongest antiproliferative activity with IC50 values ranging from 14 to 45 nM against three human cancer cell lines (MCF-7, SGC-7901 and A549), lower than that of compound 4. Mechanistic studies indicated that compound 9a could inhibit tubulin polymerization, destroy the microtubule skeleton, block the cell cycle in G2/M phase, induce cancer cell apoptosis, prevent cancer cell migration and colony formation. Moreover, compound 9a significantly inhibited tumor growth in vivo without observable toxicity in the mice 4T1 xenograft tumor model. In conclusion, this report shows a successful case of the structure-based design approach of a potent tubulin polymerization inhibitor for cancer treatment.

Electroactive nanofibrous membrane with antibacterial and deodorizing properties for air filtration.

Water vapor from respiration can severely accelerate the charge dissipation of the face mask, reducing filtration efficiency. Moreover, the foul odor from prolonged mask wear tends to make people remove their masks, leading to the risk of infection. In this study, an electro-blown spinning electroactive nanofibrous membrane (Zn/CB@PAN) with antibacterial and deodorization properties was prepared by adding zinc (Zn) and carbon black (CB) nanoparticles to the polyacrylonitrile (PAN) nanofibers, respectively. The filtration efficiency of Zn/CB@PAN for PM0.3 was > 99% and could still maintain excellent durability within 4 h in a high-humidity environment (25 â„ƒ and RH = 95%). Moreover, the bacterial interception rate of the Zn/CB@PAN could reach 99.99%, and it can kill intercepted bacteria. In addition, the deodorization rate of Zn/CB@PAN in the moist state for acetic acid was 93.75% and ammonia was 95.23%, respectively. The excellent filtering, antibacterial, and deodorizing performance of Zn/CB@PAN can be attributed to the synergistic effect of breath-induced Zn/CB galvanic couples' electroactivity, released metal ions, and generated reactive oxygen species. The developed Zn/CB@PAN could capture and kill airborne environmental pathogens under humid environments and deodorize odors from prolonged wear, holding promise for broad applications as personal protective masks.

Association between electrocardiographic abnormalities and flood exposure among middle-aged and elderly people: A national longitudinal study in China.

BACKGROUND: Flooding has become more frequent and intensive due to climate change, particularly in Asian countries. However, evidence on the long-term health effects of floods from large-scale studies on the vulnerable aged population in China is insufficient. This study analyzed the long-term effects of exposure to flood on electrocardiographic (ECG) abnormalities, a commonly used indicator of cardiovascular disease (CVD) screening, in middle-aged and elderly people. METHOD: We evaluated the Chinese National Stroke Screening Survey data of 80,711 follow-up records from 38,375 participants aged > 40 years with two or more visits between 2013 and 2018 in this longitudinal study. Flood exposure was assessed as the presence of a satellite-detected flooded area within 500 m of the residence within 5 years before the survey date. The association between ECG abnormalities and flood exposure was analyzed using a random effects model with multiple adjustments. As age is an important CVD risk factor, a varying-coefficient function was derived to estimate the nonlinear modifying effect of age on the association between ECG abnormalities and flood exposure. The strata-specific associations between ECG abnormalities and flood exposure were applied to characterize vulnerability to flood. RESULTS: The fully adjusted model suggested that flood exposure was associated with an increased risk for ECG abnormalities among the middle-aged and elderly population (odds ratio [OR] 1.74, 95 % confidence interval [CI] 1.49, 2.03). The ORs of flood exposure for ECG suggesting atrial fibrillation, ST depression, and left ventricular hypertrophy were 1.85 (95 % CI 1.16, 2.94), 6.92 (95 % CI 5.23, 9.16), and 1.55 (95 % CI 0.66, 3.65), respectively. These associations were generally robust in various subpopulations, while a sublinear curve for the negative modifying effect of age was observed on the population vulnerability to flood. CONCLUSION: Flood exposure was associated with an increased long-term risk for an ECG abnormality. The need for effective measures to mitigate vulnerability to flood is not negligible in China.

Plasmablastic lymphoma: current knowledge and future directions.

Plasmablastic lymphoma (PBL) is an aggressive non-Hodgkin lymphoma associated with HIV infection and immunodeficiency. However, PBL can also be seen immunocompetent individuals in recent studies. PBL was characterized by distinct clinical and pathological features, such as plasmablastic morphology and universal expression of plasma cell markers. The clinicopathologic features were different between HIV-negative and HIV-positive patients. Gene expression analysis identified the unique molecular feature in PBL, including frequent c-MYC rearrangement and downregulation of BCR signaling pathway. Despite the recent advances in the treatment of PBL, the prognosis of PBL patients remains dismal. The objectives of this review are to summarize the current knowledge on the epidemiology, molecular profiles, clinical and pathological features, differential diagnosis, treatment strategies, prognostic factors, and potential novel therapeutic approaches in PBL patients.

A theoretical study of the mechanism of cationic polymerization of isobutylene catalysed by EtAlCl2/t-BuCl with bis(2-chloroethyl)ether in hexanes.

The mechanism of cationic polymerization of isobutylene catalyzed by t-BuCl/ethylaluminum dichloride (EADC) combined with bis(2-chloroethyl)ether (CEE) in n-hexane solvent has been investigated using ab initio molecular dynamics (AIMD) and metadynamics (MTD) simulations. The results indicated that the polyisobutylene (PIB) initiation stage involves a clear two-step mechanism. Calculation of the free energy landscapes of the other two ether reactions reveals that the energy barriers of diisopropyl ether (i-Pr2O) and 2-chloroethyl ethyl ether (CEEE) are much higher than those of CEE, which is consistent with the experimental results. During the chain propagation phase, the required free energy barrier gradually decreases and tends to reach equilibrium as the chain length increases. Finally, the oxonium mechanism during the chain initiation stage was investigated by calculating the 1H NMR spectra and MTD simulation. Our calculations can confirm that the existence of tert-butyloxonium ions during the reaction is possible. Their contribution to the whole reaction is further discussed.

Generating active metal/oxide reverse interfaces through coordinated migration of single atoms.

Identification of active sites in catalytic materials is important and helps establish approaches to the precise design of catalysts for achieving high reactivity. Generally, active sites of conventional heterogeneous catalysts can be single atom, nanoparticle or a metal/oxide interface. Herein, we report that metal/oxide reverse interfaces can also be active sites which are created from the coordinated migration of metal and oxide atoms. As an example, a Pd1/CeO2 single-atom catalyst prepared via atom trapping, which is otherwise inactive at 30 °C, is able to completely oxidize formaldehyde after steam treatment. The enhanced reactivity is due to the formation of a Ce2O3-Pd nanoparticle domain interface, which is generated by the migration of both Ce and Pd atoms on the atom-trapped Pd1/CeO2 catalyst during steam treatment. We show that the generation of metal oxide-metal interfaces can be achieved in other heterogeneous catalysts due to the coordinated mobility of metal and oxide atoms, demonstrating the formation of a new active interface when using metal single-atom material as catalyst precursor.

Yin Yang 1 expression predicts a favourable survival in diffuse large B-cell lymphoma.

Aims: Yin Yang 1 (YY1) is a multifunctional transcription factor that plays an important role in tumour development and progression, while its clinical significance in diffuse large B-cell lymphoma (DLBCL) remains largely unexplored. This study aimed to investigate the expression and clinical implications of YY1 in DLBCL. Methods: YY1 expression in 198 cases of DLBCL was determined using immunohistochemistry. The correlation between YY1 expression and clinicopathological parameters as well as the overall survival (OS) and progression-free survival (PFS) of patients was analyzed. Results: YY1 protein expression was observed in 121 out of 198 (61.1 %) DLBCL cases. YY1 expression was significantly more frequent in cases of the GCB subgroup than in the non-GCB subgroup (P = 0.005). YY1 was positively correlated with the expression of MUM1, BCL6, pAKT and MYC/BCL2 but was negatively associated with the expression of CXCR4. No significant relationships were identified between YY1 and clinical characteristics, including age, sex, stage, localization, and B symptoms. Univariate analysis showed that the OS (P = 0.003) and PFS (P = 0.005) of patients in the YY1-negative group were significantly worse than those in the YY1-positive group. Multivariate analysis indicated that negative YY1 was a risk factor for inferior OS (P < 0.001) and PFS (P = 0.017) independent of the international prognostic index (IPI) score, treatment and Ann Arbor stage. Furthermore, YY1 is more powerful for stratifying DLBCL patients into different risk groups when combined with MYC/BCL2 double-expression (DE) status. Conclusions: YY1 was frequently expressed in DLBCL, especially in those of GCB phenotype and with MYC/BCL2-DE. As an independent prognostic factor, YY1 expression could predict a favourable outcome in DLBCL. In addition, a complex regulatory mechanism might be involved in the interactions between YY1 and MYC, pAKT as well as CXCR4 in DLBCL, which warrants further investigation.

Oasis of the deep: Cold-water corals of the South China Sea.

Cold-water coral (CWC) communities are biodiversity hotspots on the world's deep seafloor. Although deep-sea corals in the South China Sea (SCS) have been reported before, they are only sporadic. A comprehensive and systematic understanding of the CWC in the SCS would forge the basis for future protection. Here we conducted the first systematic survey on the CWCs in the following six broad-scale sub-regions, from the northwest and northeast slopes to the seamounts in the western and central basins of the SCS, through twenty-four dives of the human-occupied vehicle ShenhaiYongshi. Statistical analysis provided detailed information on the distribution, abundance, size, diversity, and density of CWCs and the in situ environmental conditions supporting coral habitats. We found that the SCS hosted highly diversified coral communities, including twelve genera of gorgonians, six genera of black corals, and one genus of stony corals. The differences in the spatial distribution patterns of coral communities suggested that several environmental variables (depth, temperature, salinity, substrate, and geomorphology) might influence the development of CWCs in the SCS. The intermediate water layer of the SCS appeared to provide suitable habitat for deep-sea coral communities and potentially promoted connectivity. Furthermore, differences between sub-regions within the SCS may be an important factor responsible for the biogeographic patterns of CWCs. These sub-regions of CWCs were observed to range from 0.004 to 0.622 corals m-2, with an average of 0.139 corals m-2. The mean density of CWCs in the SCS was relatively high compared to well-studied CWC hotspots. Overall, the results revealed the significance of the SCS as an important CWC hotspot in the world. These findings provide a fundamental basis for the protection of deep-sea coral assemblages in the SCS.

The biology and treatment of Epstein-Barr virus-positive diffuse large B cell lymphoma, NOS.

EBV positive Diffuse Large B-cell lymphoma, not otherwise specified (EBV+DLBCL-NOS) referred to DLBCL with expression of EBV encoded RNA in tumor nucleus. EBV+DLBCL-NOS patients present with more advanced clinical stages and frequent extranodal involvement. Although rituximab-containing immunochemotherapy regimens can significantly improve outcomes in patients with EBV+DLBCL, the best first-line treatment needs to be further explored. Due to the relatively low incidence and regional variation of EBV+DLBCL-NOS, knowledge about this particular subtype of lymphoma remains limited. Some signaling pathways was abnormally activated in EBV+DLBCL-NOS, including NF-κB and JAK/STAT pathways) and other signal transduction pathways. In addition, immune processes such as interferon response, antigen-presenting system and immune checkpoint molecule abnormalities were also observed. Currently, chimeric antigen receptor T-cell (CAR-T) therapy, chemotherapy combined with immunotherapy and novel targeted therapeutic drugs are expected to improve the prognosis of EBV+DLBCL-NOS patients, but more studies are needed to confirm this.

Cotton fiber-based dressings with wireless electrical stimulation and antibacterial activity for wound repair.

Although cotton dressing is one of the most commonly used wound management materials, it lacks antimicrobial and healing-promoting activity. This work developed a multilayer electroactive composite cotton dressing (Ag/Zn@Cotton/Paraffin) with exudate-activated electrical stimulation and antibacterial activity by the green and sustainable magnetron-sputtering and spraying methods. The inner hydrophilic layer of the cotton dressing was magnetron sputtered with silver/zinc galvanic couple arrays (Ag/Zn), which can be activated by wound exudate, generating an electrical stimulation (ES) into the wound. The Ag/Zn@Cotton showed efficient antibacterial activities against S. aureus and E. coli. Meanwhile, the paraffin-sprayed outer surface showed excellent antibacterial adhesion rates for S. aureus (99.82 %) and E. coli (97.92 %). The in vitro cell experiments showed that the ES generated by Ag/Zn@Cotton/Paraffin increased the migration of fibroblasts, and the in vivo mouse model indicated that the Ag/Zn@Cotton/Paraffin could enhance wound healing via re-epithelialization, inflammatory inhibition, collagen deposition, and angiogenesis. MTT method and live/dead staining showed that Ag/Zn@Cotton/Paraffin had no significant cytotoxic effects. This work may shed some light on designing and fabricating multi-functional electroactive composited dressings based on traditional biomedical textiles.

Simultaneous high-resolution whole-brain MR spectroscopy and [18F]FDG PET for temporal lobe epilepsy.

PURPOSE: Precise lateralizing the epileptogenic zone in patients with drug-resistant mesial temporal lobe epilepsy (mTLE) remains challenging, particularly when routine MRI scans are inconclusive (MRI-negative). This study aimed to investigate the synergy of fast, high-resolution, whole-brain MRSI in conjunction with simultaneous [18F]FDG PET for the lateralization of mTLE. METHODS: Forty-eight drug-resistant mTLE patients (M/F 31/17, age 12-58) underwent MRSI and [18F]FDG PET on a hybrid PET/MR scanner. Lateralization of mTLE was evaluated by visual inspection and statistical classifiers of metabolic mappings against routine MRI. Additionally, this study explored how disease status influences the associations between altered N-acetyl aspartate (NAA) and FDG uptake using hierarchical moderated multiple regression. RESULTS: The high-resolution whole-brain MRSI data offers metabolite maps at comparable resolution to [18F]FDG PET. Visual examinations of combined MRSI and [18F]FDG PET showed an mTLE lateralization accuracy rate of 91.7% in a 48-patient cohort, surpassing routine MRI (52.1%). Notably, out of 23 MRI-negative mTLE, combined MRSI and [18F]FDG PET helped detect 19 cases. Logistical regression models combining hippocampal NAA level and FDG uptake improved lateralization performance (AUC=0.856), while further incorporating extrahippocampal regions such as amygdala, thalamus, and superior temporal gyrus increased the AUC to 0.939. Concurrent MRSI/PET revealed a moderating influence of disease duration and hippocampal atrophy on the association between hippocampal NAA and glucose uptake, providing significant new insights into the disease's trajectory. CONCLUSION: This paper reports the first metabolic imaging study using simultaneous high-resolution MRSI and [18F]FDG PET, which help visualize MRI-unidentifiable lesions and may thus advance diagnostic tools and management strategies for drug-resistant mTLE.