Mapping the evolution of PET/MR research: a bibliometric analysis of publication trends, leading contributors, and conceptual frameworks (2011-2023).

BACKGROUND: Positron emission tomography-magnetic resonance imaging (PET/MR) is a cutting-edge hybrid imaging technology with the potential to revolutionize medical diagnosis. This bibliometric study aims to map the research landscape of PET/MR by analyzing a curated set of Web of Science Core Collection documents from 2011 to 2023. METHODS: We conducted a bibliometric analysis to map the research landscape of PET/MR, leveraging a curated dataset of 3,600 documents retrieved from the Web of Science Core Collection spanning the period from 2011 to 2023. We employed quantitative methods to assess the quantity and distribution of PET/MR studies, including patterns of change, research status, and directions. Additionally, we utilized VOSviewer software to conduct keyword co-occurrence analysis, explore collaborative networks among authors and institutions, and identify influential journals in the field. RESULTS: Results: The analysis reveals several key insights: (1) a significant increase in the number of PET/MR publications over the past 12 years, highlighting the growing interest and activity in this field; (2) the United States and Germany as the leading countries in terms of research output and collaboration, with a growing presence of other countries such as China; (3) the Journal of Nuclear Medicine and the European Journal of Nuclear Medicine and Molecular Imaging as the most influential journals in the field; (4) a shift in research focus from imaging techniques to clinical applications, with an increasing emphasis on prostate cancer, PSMA, and FDG imaging. CONCLUSIONS: This study provides a comprehensive overview of PET/MR research, identifying prominent trends, key researchers, and influential works. Based on these findings, we propose recommendations for future research directions in this rapidly evolving field.

A Small-molecule Antagonist Radiotracer for Positron Emission Tomography Imaging of the Mu Opioid Receptor.

The opioid crisis is a catastrophic health emergency catalyzed by the misuse of opioids that target and activate the mu opioid receptor. Traditional radioligands used to study the mu opioid receptor are often tightly regulated owing to their abuse and respiratory depression potential. In the present study, we sought to design and characterize a library of 24 non-agonist ligands for the mu opioid receptor. Ligands were evaluated for the binding affinity, intrinsic activity, and predicted blood-brain barrier permeability. Several ligands demonstrated single-digit nM binding affinity for the mu opioid receptor while also demonstrating selectivity over the delta and kappa opioid receptors. The antagonist behavior of 1A and 3A at the mu opioid receptor indicate that these ligands would likely not induce opioid-dependent respiratory depression. Therefore, these ligands can enable a safer means to interrogate the endogenous opioid system. Based on binding affinity, selectivity, and potential off-target binding, [ 11 C] 1A was prepared via metallophotoredox of the aryl-bromide functional group to [ 11 C]methyl iodide. The nascent radiotracer demonstrated brain uptake in a rhesus macaque model and accumulation in the caudate and putamen. Naloxone was able to reduce [ 11 C] 1A binding, though the interactions were not as pronounced as naloxone's ability to displace [ 11 C]carfentanil. These results suggest that GSK1521498 and related congeners are amenable to radioligand design and can offer a safer way to query opioid neurobiology.

PET Imaging with [18F]ROStrace Detects Oxidative Stress and Predicts Parkinson's Disease Progression in Mice.

Although the precise molecular mechanisms responsible for neuronal death and motor dysfunction in late-onset Parkinson's disease (PD) are unknown, evidence suggests that mitochondrial dysfunction and neuroinflammation occur early, leading to a collective increase in reactive oxygen species (ROS) production and oxidative stress. However, the lack of methods for tracking oxidative stress in the living brain has precluded its use as a potential biomarker. The goal of the current study is to address this need through the evaluation of the first superoxide (O2•-)-sensitive radioactive tracer, [18F]ROStrace, in a model of late-onset PD. To achieve this goal, MitoPark mice with a dopaminergic (DA) neuron-specific deletion of transcription factor A mitochondrial (Tfam) were imaged with [18F]ROStrace from the prodromal phase to the end-stage of PD-like disease. Our data demonstrate [18F]ROStrace was sensitive to increased oxidative stress during the early stages of PD-like pathology in MitoPark mice, which persisted throughout the disease course. Similarly to PD patients, MitoPark males had the most severe parkinsonian symptoms and metabolic impairment. [18F]ROStrace retention was also highest in MitoPark males, suggesting oxidative stress as a potential mechanism underlying the male sex bias of PD. Furthermore, [18F]ROStrace may provide a method to identify patients at risk of Parkinson's before irreparable neurodegeneration occurs and enhance clinical trial design by identifying patients most likely to benefit from antioxidant therapies.

A tau dephosphorylation-targeting chimeraselectively recruits protein phosphatase-1 to ameliorate Alzheimer's disease and tauopathies.

Abnormal accumulation of hyperphosphorylated tau (pTau) is a major cause of neurodegeneration in Alzheimer's disease (AD) and related tauopathies. Therefore, reducing pTau holds therapeutic promise for these diseases. Here, we developed a chimeric peptide, named D20, for selective facilitation of tau dephosphorylation by recruiting protein phosphatase 1 (PP1) to tau. PP1 is one of the active phosphatases that dephosphorylates tau. In both cultured primary hippocampal neurons and mouse models for AD or related tauopathies, we demonstrated that single-dose D20 treatment significantly reduced pTau by dephosphorylation at multiple AD-related sites and total tau (tTau) levels were also decreased. Multiple-dose administration of D20 through tail vein injection in 3xTg AD mice effectively ameliorated tau-associated pathologies with improved cognitive functions. Importantly, at therapeutic doses, D20 did not cause detectable toxicity in cultured neurons, neural cells, or peripheral organs in mice. These results suggest that D20 is a promising drug candidate for AD and related tauopathies.

Kinetic Analysis and Metabolism of Poly(Adenosine Diphosphate-Ribose) Polymerase-1-Targeted 18F-Fluorthanatrace PET in Breast Cancer.

The poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) have demonstrated efficacy in ovarian, breast, and prostate cancers, but current biomarkers do not consistently predict clinical benefit. 18F-fluorthanatrace (18F-FTT) is an analog to rucaparib, a clinically approved PARPi, and is a candidate biomarker for PARPi response. This study intends to characterize 18F-FTT pharmacokinetics in breast cancer and optimize image timing for clinical trials. A secondary aim is to determine whether 18F-FTT uptake in breast cancer correlates with matched frozen surgical specimens as a reference standard for PARP-1 protein. Methods: Thirty prospectively enrolled women with a new diagnosis of breast cancer were injected with 18F-FTT and imaged dynamically 0-60 min after injection over the chest, with an optional static scan over multiple bed positions starting around 70 min. Kinetic analysis of lesion uptake was performed using blood-pool activity with population radiometabolite corrections. Normal breast and normal muscle reference tissue models were compared with PARP-1 protein expression in 10 patients with available tissue. Plasma radiometabolite concentrations and uptake in tumor and normal muscle were investigated in mouse xenografts. Results: Pharmacokinetics of 18F-FTT were well fit by Logan plot reference region models of reversible binding. However, fits of 2-tissue compartment models assuming negligible metabolite uptake were unstable. Rapid metabolism of 18F-FTT was demonstrated in mice, and similar uptake of radiometabolites was found in tumor xenografts and normal muscle. Tumor 18F-FTT distribution volume ratios relative to normal muscle reference tissue correlated with tissue PARP-1 expression (P < 0.02, n = 10). The tumor-to-normal muscle ratio from a 5-min frame between 50 and 60 min after injection, a potential static scan protocol, closely corresponded to the distribution volume ratio relative to normal muscle and correlated to PARP-1 expression (P < 0.02, n = 10). Conclusion: This study of PARPi analog 18F-FTT showed that uptake kinetics in vivo corresponded to expression of PARP-1 and that 18F-FTT quantitation is influenced by radiometabolites that are increasingly present late after injection. Radiometabolites can be controlled by using optimal image acquisition timing or normal muscle reference tissue modeling in dynamic imaging or a tumor-to-normal muscle ratio. Optimal image timing for tumor-to-normal muscle quantification in humans appears to be between 50 and 60 min after injection. Therefore, a clinically practical static imaging protocol commencing 45-55 min after injection may sufficiently balance 18F-FTT uptake with background clearance and radiometabolite interference for quantitative interpretation of PARP-1 expression in vivo.

Automation of simplified two-step radiolabeling via ditosylate synthon for 18F-labeled radiotracers using AllinOne module.

Direct fluorination of a tosylate or mesylate precursor has been a wide-spread and reliable way for radio-fluorination. This approach can be difficult to achieve when the precursor cannot be easily obtained or is chemically unstable. A possible alternative method is to radiolabel ethylene ditosylate or 1,3-propanediol di-p-tosylate to form a radiofluorinated synthon. Here we present the automation of a simplified and reliable approach for the two-step fluorination using [18F]FP-TMP, an analog of antibacterial agent trimethoprim. We demonstrate the feasibility of purifying the fluorinated synthon via filtration, and one final HPLC purification on a commercially available Trasis AllinOne module. The overall reaction time for the two-step reaction is around 90 min andthe decay-corrected yield for more than fifty preparations of [18F]FP-TMP is 22 ± 5 % with high radiochemical purity (≥ 90 %) and specific activities (147 ± 107 GBq/µmol). All batches passed pre-established quality control specifications, demonstrating the utility of using this method in tracer syntheses that meet good manufacturing practice (GMP) requirement. This method can be adopted to the syntheses of other radiotracers, such as [18F]FE-TMP, (+)-[18F]F-PHNO and [18F]FFMZ.

An inhalable nanoparticle enabling virulence factor elimination and antibiotics delivery for pneumococcal pneumonia therapy.

Streptococcus pneumoniae (S. pneumoniae) is a major cause of community-acquired pneumonia. Current standard clinical therapies mainly focus on combating S. pneumoniae through antibiotics. However, the limited delivery of antibiotics and the undetoxified hydrogen peroxide (H2O2) virulence factor secreted by S. pneumoniae impede the therapeutic outcomes. Here we report an inhalable catalase (CAT)-tannic acid (TA) nanoassembly for local antibiotic (levofloxacin) delivery and simultaneously neutralizing the secreted H2O2 virulence factors to treat pneumococcal pneumonia. After aerosol inhalation, the inhalable formulation (denoted as CT@LVX) effectively accumulates in lung tissues through TA-mediated mucoadhesion. CAT can reduce alveolar epithelial cells apoptosis by catalyzing the decomposition of accumulated H2O2 in the infected lung tissues. In synergy with antibiotic LVX-mediated S. pneumoniae elimination, CT@LVX significantly decreases lung injury companied with reduced inflammatory, resulting in 100 % survival of mice with pneumonia. In a clinically isolated S. pneumoniae strain-induced pneumonia mouse model, CT@LVX also shows superior outcomes compared to the traditional antibiotic treatment, highlighting its potential clinical application prospects.

Research note: characteristics of blaNDM and mcr-1 co-producing Escherichia coli from retail chicken meat.

Carbapenems and colistin are vital antimicrobials used to treat Enterobacteriaceae-caused infections. The present study aimed to characterize the coexistence mechanism of carbapenem and colistin resistance in an Escherichia coli isolated from retail chicken meat. A total of 4 E. coli isolates co-harboring carbapenem resistance gene blaNDM (2 E. coli isolates with blaNDM-5 and 2 with blaNDM-9) and colistin resistance gene mcr-1. Antimicrobial susceptibility testing exhibited that all the 4 E. coli strains had multidrug resistance profile and consistent with the resistance genes they carried. MLST showed that 3 E. coli isolates belonged to a pathogenic E. coli lineage ST354, which is closely associated with human infections and pose a serious threat to public health. Whole genome sequencing (WGS) showed that 4 mcr-1-positive plasmids with sizes of 60.4 kb to 67.4 kb all belonged to the IncI2 type. A total of 5 blaNDM-harboring plasmids ranged from 99.0 kb to 138.3 kb, among which 4 plasmids belonged to unknow type and only pCS5L-NDM belonged to IncFIA/IncFIB group of hybrid plasmids, a novel carrier for blaNDM. Comparative analysis exhibited that the mcr-1 or blaNDM-carrying plasmids of E. coli strains from chicken meat showed high identity with that from Enterobacteriaceae of human origin, which indicated the risk of mcr-1 or blaNDM dissemination from retail meat to human. The simultaneous occurrence of mcr-1 and blaNDM in E. coli emphasizes the significant of antimicrobial resistance surveillance in retail meat.

Spatiotemporal analysis and seasonality of tuberculosis in Pudong New Area of Shanghai, China, 2014-2023.

BACKGROUND: Spatiotemporal analysis is a vital method that plays an indispensable role in monitoring epidemiological changes in diseases and identifying high-risk clusters. However, there is still a blank space in the spatial and temporal distribution of tuberculosis (TB) incidence rate in Pudong New Area, Shanghai. Consequently, it is crucial to comprehend the spatiotemporal distribution of TB in this district, this will guide the prevention and control of TB in the district. METHODS: Our research used Geographic Information System (GIS) visualization, spatial autocorrelation analysis, and space-time scan analysis to analyze the TB incidence reported in the Pudong New Area of Shanghai from 2014 to 2023, and described the spatiotemporal clustering and seasonal hot spot distribution of TB incidence. RESULTS: From 2014 to 2023, the incidence of TB in the Pudong New Area decreased, and the mortality was at a low level. The incidence of TB in different towns/streets has declined. The spatial autocorrelation analysis revealed that the incidence of TB was spatially clustered in 2014, 2016-2018, and 2022, with the highest clusters in 2014 and 2022. The high clustering area was mainly concentrated in the northeast. The space-time scan analysis indicated that the most likely cluster was located in 12 towns/streets, with a period of 2014-2018 and a radiation radius of 15.74 km. The heat map showed that there was a correlation between TB incidence and seasonal variations. CONCLUSIONS: From 2014 to 2023, the incidence of TB in the Pudong New Area of Shanghai declined, but there were spatiotemporal clusters and seasonal correlations in the incidence area. Local departments should formulate corresponding intervention measures, especially in high-clustering areas, to achieve accurate prevention and control of TB within the most effective time and scope.

Periphery Biomarkers Predicting Conversion of Type 2 Diabetes to Pre-Alzheimer-Like Cognitive Decline: A Multicenter Follow-Up Study.

Background: The prevalence of Alzheimer's disease (AD) is increasing, therefore, identifying biomarkers to predict those vulnerable to AD is imperative. Type 2 diabetes (T2D) serves as an independent risk factor for AD. Early prediction of T2D patients who may be more susceptible to AD, so as to achieve early intervention, is of great significance to reduce the prevalence of AD. Objective: To establish periphery biomarkers that could predict conversion of T2D into pre-AD-like cognitive decline. Methods: A follow-up study was carried out from 159 T2D patients at baseline. The correlations of cognitive states (by MMSE score) with multi-periphery biomarkers, including APOE genotype, plasma amyloid-ß level, platelet GSK-3ß activity, and olfactory score were analyzed by logistic regression. ROC curve was used for establishing the prediction model. Additionally, MRI acquired from 38 T2D patients for analyzing the correlation among cognitive function, biomarkers and brain structure. Results: Compared with the patients who maintained normal cognitive functions during the follow-up period, the patients who developed MCI showed worse olfactory function, higher platelet GSK-3ß activity, and higher plasma Aß42/Aß40 ratio. We conducted a predictive model which T2D patients had more chance of suffering from pre-AD-like cognitive decline. The MRI data revealed MMSE scores were positively correlated with brain structures. However, platelet GSK-3ß activity was negatively correlated with brain structures. Conclusions: Elevated platelet GSK-3ß activity and plasma Aß42/Aß40 ratio with reduced olfactory function are correlated with pre-AD-like cognitive decline in T2D patients, which used for predicting which T2D patients will convert into pre-AD-like cognitive decline in very early stage.

A new tau dephosphorylation-targeting chimera for the treatment of tauopathies.

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer's disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

Identification of T2W hypointense ring as a novel noninvasive indicator for glioma grade and IDH genotype.

BACKGROUND: This study aimed to evaluate the T2W hypointense ring and T2-FLAIR mismatch signs in gliomas and use these signs to construct prediction models for glioma grading and isocitrate dehydrogenase (IDH) mutation status. METHODS: Two independent radiologists retrospectively evaluated 207 glioma patients to assess the presence of T2W hypointense ring and T2-FLAIR mismatch signs. The inter-rater reliability was calculated using the Cohen's kappa statistic. Two logistic regression models were constructed to differentiate glioma grade and predict IDH genotype noninvasively, respectively. Receiver operating characteristic (ROC) analysis was used to evaluate the developed models. RESULTS: Of the 207 patients enrolled (119 males and 88 females, mean age 51.6 ± 14.8 years), 45 cases were low-grade gliomas (LGGs), 162 were high-grade gliomas (HGGs), 55 patients had IDH mutations, and 116 were IDH wild-type. The number of T2W hypointense ring signs was higher in HGGs compared to LGGs (p < 0.001) and higher in the IDH wild-type group than in the IDH mutant group (p < 0.001). There were also significant differences in T2-FLAIR mismatch signs between HGGs and LGGs, as well as between IDH mutant and wild-type groups (p < 0.001). Two predictive models incorporating T2W hypointense ring, absence of T2-FLAIR mismatch, and age were constructed. The area under the ROC curve (AUROC) was 0.940 for predicting HGGs (95% CI = 0.907-0.972) and 0.830 for differentiating IDH wild-type (95% CI = 0.757-0.904). CONCLUSIONS: The combination of T2W hypointense ring, absence of T2-FLAIR mismatch, and age demonstrate good predictive capability for HGGs and IDH wild-type. These findings suggest that MRI can be used noninvasively to predict glioma grading and IDH mutation status, which may have important implications for patient management and treatment planning.

Using Gaussian accelerated molecular dynamics combined with Markov state models to explore the mechanism of action of new oral inhibitors on Complex I.

In this study, our focus was on investigating H-1,2,3-triazole derivative HP661 as a novel and highly efficient oral OXPHOS inhibitor, with its molecular-level inhibitory mechanism not yet fully understood. We selected the ND1, NDUFS2, and NDUFS7 subunits of Mitochondrial Complex I as the receptor proteins and established three systems for comparative analysis: protein-IACS-010759, protein-lead compound 10, and protein-HP661. Through extensive analysis involving 500 ns Gaussian molecular dynamics simulations, we gained insights into these systems. Additionally, we constructed a Markov State Models to examine changes in secondary structures during the motion processes. The research findings suggest that the inhibitor HP661 enhances the extensibility and hydrophilicity of the receptor protein. Furthermore, HP661 induces the unwinding of the α-helical structure in the region of residues 726-730. Notably, key roles were identified for Met37, Phe53, and Pro212 in the binding of various inhibitors. In conclusion, we delved into the potential molecular mechanisms of triazole derivative HP661 in inhibiting Complex I. These research outcomes provide crucial information for a deeper understanding of the mechanisms underlying OXPHOS inhibition, offering valuable theoretical support for drug development and disease treatment design.

Subtrochanteric fracture after core decompression for osteonecrosis of the femoral head: a case report and literature review.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common clinical disease. Improper treatment can lead to femoral head collapse and hip joint dysfunction. Core decompression is particularly important for early ONFH. However, subtrochanteric fractures after core decompression cause some clinical problems. CASE PRESENTATION: This article describes a 34-year-old male patient with early ONFH. After core decompression, he suffered a subtrochanteric fracture of the femur while bearing weight on the affected limb when going up stairs. He was subsequently treated with open reduction and intramedullary nail fixation. CONCLUSION: When core decompression is used to treat ONFH, the location or size of the drill hole, whether a tantalum rod or bone is inserted, and partial weight-bearing of the affected limb may directly affect whether a fracture occurs after surgery. It is hoped that this case report can provide a reference for clinical orthopedic surgeons in the treatment of early ONFH.

Positron Emission Tomography with [18F]ROStrace Reveals Progressive Elevations in Oxidative Stress in a Mouse Model of Alpha-Synucleinopathy.

The synucleinopathies are a diverse group of neurodegenerative disorders characterized by the accumulation of aggregated alpha-synuclein (aSyn) in vulnerable populations of brain cells. Oxidative stress is both a cause and a consequence of aSyn aggregation in the synucleinopathies; however, noninvasive methods for detecting oxidative stress in living animals have proven elusive. In this study, we used the reactive oxygen species (ROS)-sensitive positron emission tomography (PET) radiotracer [18F]ROStrace to detect increases in oxidative stress in the widely-used A53T mouse model of synucleinopathy. A53T-specific elevations in [18F]ROStrace signal emerged at a relatively early age (6-8 months) and became more widespread within the brain over time, a pattern which paralleled the progressive development of aSyn pathology and oxidative damage in A53T brain tissue. Systemic administration of lipopolysaccharide (LPS) also caused rapid and long-lasting elevations in [18F]ROStrace signal in A53T mice, suggesting that chronic, aSyn-associated oxidative stress may render these animals more vulnerable to further inflammatory insult. Collectively, these results provide novel evidence that oxidative stress is an early and chronic process during the development of synucleinopathy and suggest that PET imaging with [18F]ROStrace holds promise as a means of detecting aSyn-associated oxidative stress noninvasively.

The Effects of Perineural Dexamethasone on Rebound Pain After Nerve Block in Patients With Unicompartmental Knee Arthroplasty: A Randomized Controlled Trial.

OBJECTIVES: A single nerve block provides excellent analgesia in a short time, but rebound pain after the nerve block dissipates has attracted researchers' attention. The aim of this study was to evaluate the effect of perineural dexamethasone on rebound pain after sciatic nerve block and femoral nerve block in patients undergoing unicompartmental knee arthroplasty (UKA). METHODS: In a double-blinded fashion, we recruited 72 patients undergoing UKA, each of whom received sciatic and femoral nerve block. Patients were randomly assigned to 2 groups (n=36): X (ropivacaine only) and D (ropivacaine combined with dexamethasone). The primary outcome was the incidence of rebound pain. The secondary outcomes were rebound pain score, the duration of rebound pain, the duration of nerve block, pain score, sufentanil consumption and rescue analgesic, patient-controlled intravenous analgesia, distance walked, sleep quality score, C-reactive protein levels, and adverse effects. RESULTS: Compared with group X, the incidence of rebound pain in group D was higher, the rebound pain score was higher and the duration of the nerve block was prolonged ( P <0.05). At 12, 16, and 20 hours postoperatively, the pain scores at rest in group D were lower. At 32 and 36 hours postoperatively, the pain scores at rest in group D were higher ( P <0.05). Furthermore, patients in group D had lower levels of C-reactive protein after surgery ( P <0.05). DISCUSSION: The addition of dexmedetomidine to ropivacaine for UKA effectively prolonged the duration of nerve block and decreased C-reactive protein levels, but increased the incidence of rebound pain and rebound pain score, and had no beneficial effects on the postoperative analgesia.

Identification of osteoporosis ferroptosis-related markers and potential therapeutic compounds based on bioinformatics methods and molecular docking technology.

RESEARCH BACKGROUND AND PURPOSE: Osteoporosis (OP) is one of the most common bone diseases worldwide, characterized by low bone mineral density and susceptibility to pathological fractures, especially in postmenopausal women and elderly men. Ferroptosis is one of the newly discovered forms of cell death regulated by genes in recent years. Many studies have shown that ferroptosis is closely related to many diseases. However, there are few studies on ferroptosis in osteoporosis, and the mechanism of ferroptosis in osteoporosis is still unclear. This study aims to identify biomarkers related to osteoporosis ferroptosis from the GEO (Gene Expression Omnibus) database through bioinformatics technology, and to mine potential therapeutic small molecule compounds through molecular docking technology, trying to provide a basis for the diagnosis and treatment of osteoporosis in the future. MATERIALS AND METHODS: We downloaded the ferroptosis-related gene set from the FerrDb database ( http://www.zhounan.org/ferrdb/index.html ), downloaded the data sets GSE56815 and GSE7429 from the GEO database, and used the R software "limma" package to screen differentially expressed genes (DEGs) from GSE56815, and intersected with the ferroptosis gene set to obtain ferroptosis-related DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by the R software "clusterProfiler" package. The random forest model was further screened to obtain essential ferroptosis genes. R software "corrplot" package was used for correlation analysis of essential ferroptosis genes, and the Wilcox test was used for significance analysis. The lncRNA-miRNA-mRNA-TF regulatory network was constructed using Cytoscape software. The least absolute shrinkage and selection operator (LASSO) was used to construct a disease diagnosis model, and a Receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic performance, and then GSE7429 was used to verify the reliability of the diagnosis model. Molecular docking technology was used to screen potential small molecule compounds from the Drugbank database. Finally, a rat osteoporosis model was constructed, and peripheral blood mononuclear cells were extracted for qRT-PCR detection to verify the mRNA expression levels of crucial ferroptosis genes. RESULT: Six DEGs related to ferroptosis were initially screened out. GO function and KEGG pathway enrichment analysis showed that ferroptosis-related DEGs were mainly enriched in signaling pathways such as maintenance of iron ion homeostasis, copper ion binding function, and ferroptosis. The random forest model identified five key ferroptosis genes, including CP, FLT3, HAMP, HMOX1, and SLC2A3. Gene correlation analysis found a relatively low correlation between these five key ferroptosis genes. The lncRNA-miRNA-mRNA-TF regulatory network shows that BAZ1B and STAT3 may also be potential molecules. The ROC curve of the disease diagnosis model shows that the model has a good diagnostic performance. Molecular docking technology screened out three small molecule compounds, including NADH, Midostaurin, and Nintedanib small molecule compounds. qRT-PCR detection confirmed the differential expression of CP, FLT3, HAMP, HMOX1 and SLC2A3 between OP and normal control group. CONCLUSION: This study identified five key ferroptosis genes (CP, FLT3, HAMP, HMOX1, and SLC2A3), they were most likely related to OP ferroptosis. In addition, we found that the small molecule compounds of NADH, Midostaurin, and Nintedanib had good docking scores with these five key ferroptosis genes. These findings may provide new clues for the early diagnosis and treatment of osteoporosis in the future.

Improve the diagnosis of idiopathic normal pressure hydrocephalus by combining abnormal cortical thickness and ventricular morphometry.

Background: The primary imaging markers for idiopathic Normal Pressure Hydrocephalus (iNPH) emphasize morphological measurements within the ventricular system, with no attention given to alterations in brain parenchyma. This study aimed to investigate the potential effectiveness of combining ventricular morphometry and cortical structural measurements as diagnostic biomarkers for iNPH. Methods: A total of 57 iNPH patients and 55 age-matched healthy controls (HC) were recruited in this study. Firstly, manual measurements of ventricular morphology, including Evans Index (EI), z-Evans Index (z-EI), Cella Media Width (CMW), Callosal Angle (CA), and Callosal Height (CH), were conducted based on MRI scans. Cortical thickness measurements were obtained, and statistical analyses were performed using surface-based morphometric analysis. Secondly, three distinct models were developed using machine learning algorithms, each based on a different input feature: a ventricular morphology model (LVM), a cortical thickness model (CT), and a fusion model (All) incorporating both features. Model performances were assessed using 10-fold cross validation and tested on an independent dataset. Model interpretation utilized Shapley Additive Interpretation (SHAP), providing a visualization of the contribution of each variable in the predictive model. Finally, Spearman correlation coefficients were calculated to evaluate the relationship between imaging biomarkers and clinical symptoms. Results: iNPH patients exhibited notable differences in cortical thickness compared to HC. This included reduced thickness in the frontal, temporal, and cingulate cortices, along with increased thickness in the supracentral gyrus. The diagnostic performance of the fusion model (All) for iNPH surpassed that of the single-feature models, achieving an average accuracy of 90.43%, sensitivity of 90.00%, specificity of 90.91%, and Matthews correlation coefficient (MCC) of 81.03%. This improvement in accuracy (6.09%), sensitivity (11.67%), and MCC (11.25%) compared to the LVM strategy was significant. Shap analysis revealed the crucial role of cortical thickness in the right isthmus cingulate cortex, emerging as the most influential factor in distinguishing iNPH from HC. Additionally, significant correlations were observed between the typical triad symptoms of iNPH patients and cortical structural alterations. Conclusion: This study emphasizes the significant role of cortical structure changes in the diagnosis of iNPH, providing a novel insights for assisting clinicians in improving the identification and detection of iNPH.

A combined transcriptomics and proteomics approach to reveal the mechanism of AEE relieving hyperlipidemia in ApoE-/- mice.

Hyperlipidemia caused by abnormal lipid metabolism has reached epidemic proportions. This phenomenon is also common in companion animals. Previous studies showed that AEE significantly improves abnormal blood lipids in hyperlipidemia rats and mice, but its mechanism is still not clear enough. In this study, the mechanism and potential key pathways of AEE on improving hyperlipidemia in mice were investigated through the transcriptome and proteome study of ApoE-/- mice liver and the verification study on high-fat HepG2 cells. The results showed that AEE significantly decreased the serum TC and LDL-C levels of hyperlipidemia ApoE-/- mice, and significantly increased the enzyme activity of CYP7A1. After AEE intervention, the results of mice liver transcriptome and proteome showed that differential genes and proteins were enriched in lipid metabolism-related pathways. The results of RT-qPCR showed that AEE significantly regulated the expression of genes related to lipid metabolism in mice liver tissue. AEE significantly upregulated the protein expression of CYP7A1 in hyperlipidemia ApoE-/- mice liver tissue. The results in vitro showed that AEE significantly decreased the levels of TC and TG, and improved lipid deposition in high-fat HepG2 cells. AEE significantly increased the expression of CYP7A1 protein in high-fat HepG2 cells. AEE regulates the expression of genes related to lipid metabolism in high-fat HepG2 cells, mainly by FXR-SHP-CYP7A1 and FGF19-TFEB-CYP7A1 pathways. To sum up, AEE can significantly improve the hyperlipidemia status of ApoE-/- mice and the lipid deposition of high-fat HepG2 cells, and its main pathway is probably the bile acid metabolism-related pathway centered on CYP7A1.