The high inter-individual heterogeneity in individuals with depression limits neuroimaging studies with case-control approaches to identify promising biomarkers for individualized clinical ...decision-making. We put forward a framework integrating the normative model and non-negative matrix factorization (NMF) to quantitatively assess altered gray matter morphology in depression from a dimensional perspective. The proposed framework parses altered gray matter morphology into overlapping latent disease factors, and assigns patients distinct factor compositions, thus preserving inter-individual variability. We identified four robust disease factors with distinct clinical symptoms and cognitive processes in depression. In addition, we showed the quantitative relationship between the group-level gray matter morphological differences and disease factors. Furthermore, this framework significantly predicted factor compositions of patients in an independent dataset. The framework provides an approach to resolve neuroanatomical heterogeneity in depression.
•BS patients exhibited functional damage primarily in ipsilesional sensorimotor cortex and contralesional cerebellum.•PS patients showed functional impairment primarily in cerebellum.•Different ...patterns of secondary brain damage in different types of infarction.
We investigated the influence of lesion location on cerebral blood flow (CBF) in chronic subcortical stroke patients. Three-dimensional pseudocontinuous arterial spin labeling was employed to obtain CBF images in normal controls (NC) and patients with left hemisphere subcortical infarctions involving motor pathways. Stroke patients were divided into two subgroups based on the infarction location (basal ganglia (BS) or pontine (PS). We mapped CBF alterations in a voxel-wise manner and compared them to detect differences among groups with height-level false discovery rate correction. Regions with significant group differences were extracted to perform post hoc analyses among the BS, PS and NC groups using a general linear model with age, gender, years of education, and interval after stroke as covariates. The BS group displayed significantly increased CBF in the contralesional putamen relative to NC and significantly decreased CBF in the ipsilesional sensorimotor cortex, ipsilesional thalamus and contralesional cerebellum. The PS group displayed significantly increased CBF in the contralesional inferior frontal gyrus relative to both the NC and BS groups. Nevertheless, the PS group showed significantly decreased CBF mainly in the cerebellum. Our results suggest different alteration patterns of CBF in chronic stroke patients with different infarct locations within subcortical motor pathways, potentially providing important information for the initiation of individualized rehabilitation strategies for subcortical stroke patients involving different infarct types.
MicroRNA-34a (miR-34a) plays an essential role against tumorigenesis and progression of cancer metastasis. Here, we analyzed the expression, targets and functional effects of miR-34a on epithelial to ...mesenchymal transition-inducing transcription factors (EMT-TFs), such as TWIST1, SLUG and ZEB1/2, and an EMT-inducing protein NOTCH1 in breast cancer (BC) cell migration and invasion and its correlation with tumorigenesis and clinical outcomes. Expression of miR-34a is downregulated in human metastatic breast cancers (MBC) compared to normal breast tissues and is negatively correlated with clinicopathological features of MBC patients. Ectopic expression of miR-34a in MBC cell-line BT-549 significantly inhibits cell migration and invasion, but exhibits no clear effect on BC cell growth. We found that miR-34a is able to inactivate EMT signaling pathway with mediatory of NOTCH1, TWIST1, and ZEB1 upon 3'-UTR activity in MBC cell lines, but has no inhibitory effects on SLUG and ZEB2. Furthermore, we investigated the synergistic effects of Thymoquinone (TQ) and miR-34a together on the expression of EMT-associated proteins. Results showed that co-delivery of miR-34a and TQ is able to inactivate EMT signaling pathway by directly targeting TWIST1 and ZEB1 in BT-549 cell line, indicating that they might be a promising therapeutic combination against breast cancer metastasis. Epigenetic inactivation of the EMT-TFs/miR-34a pathway can potentially alter the equilibrium of these regulations, facilitating EMT and metastasis in BC. Altogether, our findings suggest that miR-34a alone could serve as a potential therapeutic agent for MBC, and together with TQ, their therapeutic potential is synergistically enhanced.
To examine the diagnostic advantages and clinical application value of the cinematic volume rendering technique (cVRT) when evaluating the relationship between the brachial plexus, peripheral tumor ...lesions, and blood vessels.
Seventy-nine patients with brachial plexus tumors between November 2012 and July 2022 were enrolled in our study. All patients underwent T1WI, T2WI, three-dimensional short recovery time reversal recovery fast spin-echo imaging (3D-STIR-SPACE), and the T1WI enhancement sequence. In addition, cVRT was used to render and obtain a three-dimensional model that clearly showed the location and tissue structure of the brachial plexus nerves and the tumor in all directions.
Seventy-one patients (mean age, 47.1 years; 33 males, 38 females) with tumors around the brachial plexus were included in the study. The brachial plexus nerve, surrounding tumor lesions, and vascular anatomy of all patients were well displayed with cVRT. The tumors of 37 patients manifested as unilateral or bilateral growths along the brachial plexus nerve and were fusiform, spherical, or multiple beaded; seven patients' tumors pushed against the brachial plexus nerve and were circular, lobular, or irregular; sixteen patients' tumors encircled the brachial plexus nerve and were spherical; and eleven patients' tumors infiltrated the brachial plexus nerve and had irregular morphology. The mass has a moderately uniform or uneven signal on T1WI and a high or mixed signal on T2WI. After enhancement, the signal was evenly or unevenly strengthened.
cVRT clearly showed the origin of tumors associated with the brachial plexus and their relationship with the nerves and peripheral blood vessels, providing reliable information for clinical diagnosis and treatment.
Purpose To explore the value of 3D amide proton transfer weighted imaging (APTWI) in the differential diagnosis between benign and malignant bone tumors, and to compare the diagnostic performance of ...APTWI with traditional diffusion-weighted imaging (DWI). Materials and methods Patients with bone tumors located in the pelvis or lower limbs confirmed by puncture or surgical pathology were collected from January 2021 to July 2023 in the First Affiliated Hospital of Zhengzhou University. All patients underwent APTWI and DWI examinations. The magnetization transfer ratio with asymmetric analysis at the frequency offset of 3.5 ppm MTRasym(3.5 ppm) derived by APTWI and the apparent diffusion coefficient (ADC) derived by DWI for the tumors were measured. The Kolmogorou-Smirnou and Levene normality test was used to confirm the normal distribution of imaging parameters; and the independent sample t test was used to compare the differences in MTRasym(3.5 ppm) and ADC between benign and malignant bone tumors. In addition, the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of different imaging parameters in differentiation between benign and malignant bone tumors. P<0.05 means statistically significant. Results Among 85 bone tumor patients, 33 were benign and 52 were malignant. The MTRasym(3.5 ppm) values of malignant bone tumors were significantly higher than those of benign tumors, while the ADC values were significantly lower in benign tumors. ROC analysis shows that MTRasym(3.5 ppm) and ADC values perform well in the differential diagnosis of benign and malignant bone tumors, with the area under the ROC curve (AUC) of 0.798 and 0.780, respectively. Combination of MTRasym(3.5 ppm) and ADC values can further improve the diagnostic performance with the AUC of 0.849 (sensitivity = 84.9% and specificity = 73.1%). Conclusion MTRasym(3.5 ppm) of malignant bone tumors was significantly higher than that of benign bone tumors, reflecting the abnormal increase of protein synthesis in malignant tumors. APTWI combined with DWI can achieve a high diagnostic efficacy in differentiation between benign and malignant bone tumors.
Nowadays, about 30% of magnetic resonance imaging (MRI) exams need contrast agents (CAs) to improve the sensitivity and quality of the images for accurate diagnosis. Here, a multifunctional ...nano-agent with ring-like vortex-domain iron oxide as core and gadolinium oxide as shell (vortex nanoring Fe3O4 @Gd2O3, abbreviated as VNFG) was firstly designed and prepared for highly enhanced T1-T2 dual-modality magnetic resonance imaging (MRI)-guided magnetic thermal cancer therapy. After thorough characterization, the core-shell structure of VNFG was confirmed. Moreover, the excellent heat generation property (SAR=984.26 W/g) of the proposed VNFG under alternating magnetic fields was firmly demonstrated. Furthermore, both in vitro and in vivo studies have revealed a good preliminary indication of VNFG’s biological compatibility, dual-modality enhancing feature and antitumor efficacy. This work demonstrates that the proposed VNFG can be a high-performance tumor diagnosis and theranostic treatment agent and may have great potential for clinical application in the future.
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•A highly efficient T1-T2 dual-modality MRI contrast agent (VNFG) was synthesized by multistep reactions.•VNFG showed both extremely high R1 and R2, as well as an ideal low ratio (r2/r1).•The excellent heat generation property (SAR=984.26 W/g) of VNFG under different alternating magnetic fields was firmly demonstrated.•In vitro and in vivo studies demonstrated the ability of VNFG as an efficient theranostic agent for MRI-guided magnetic thermal cancer ablation.
•Patients with first-episode schizophrenia had significantly decreased QSM values in the bilateral substantia nigra, left red nucleus and left thalamus.•Patients with first-episode schizophrenia had ...significantly increased regional volumes in the bilateral putamen and bilateral substantia nigra.•QSM provides superior sensitivity over R2* mapping in the evaluation of schizophrenia-related iron alterations.•QSM values in regions that showed intergroup differences did not exhibited significant correlations with PANSS scores.
Decreased serum ferritin level was recently found in schizophrenia. Whether the brain iron concentration in schizophrenia exists abnormality is of research significance. Quantitative susceptibility mapping (QSM) was used in this study to assess brain iron changes in the grey matter nuclei of patients with first-episode schizophrenia.
The local ethics committee approved the study, and all subjects gave written informed consent. Thirty patients with first-episode schizophrenia and 30 age and gender-matched healthy controls were included in this study. QSM and effective transverse relaxation rate (R2*) maps were reconstructed from a three-dimensional multi-echo gradient-echo sequence. The inter-group differences of regional QSM values, R2* values and volumes were calculated in the grey matter nuclei, including bilateral caudate nucleus, putamen, globus pallidus, substantia nigra, red nucleus, and thalamus. The diagnostic performance of QSM and R2* was evaluated using receiver operating characteristic curve. The correlations between regional iron variations and clinical PANSS (Positive and Negative Syndrome Scale) scores were assessed using partial correlation analysis.
Compared to healthy controls, patients with first-episode schizophrenia had significantly decreased QSM values (less paramagnetic) in the bilateral substantia nigra, left red nucleus and left thalamus (p < 0.05, FDR correction). QSM proved more sensitive than R2* regarding inter-group differences. The highest diagnostic performance for first-episode schizophrenia was observed in QSM value of the left substantia nigra (area under the curve, AUC = 0.718, p = 0.004). Regional volumes of bilateral putamen and bilateral substantia nigra were increased (p < 0.05, FDR correction) in first-episode schizophrenia. However, both QSM and R2* values did not show significant correlations with PANSS scores (p > 0.05).
This study reveals decreased iron concentration in grey matter nuclei of patients with first-episode schizophrenia. QSM provides superior sensitivity over R2* in the evaluation of schizophrenia-related brain iron changes. It demonstrated that QSM may be a potential biomarker for further understanding the pathophysiological mechanism of first-episode schizophrenia.
Functional metal doping endows fluorescent carbon dots with richer physical and chemical properties, greatly expanding their potential in the biomedical field. Nonetheless, fabricating carbon dots ...with integrated functionality for diagnostic and therapeutic modalities remains challenging. Herein, we develop a simple strategy to prepare Gd/Ru bimetallic doped fluorescent carbon dots (Gd/Ru-CDs) via a one-step microwave-assisted method with Ru(dcbpy)
Cl
, citric acid, polyethyleneimine, and GdCl
as precursors. Multiple techniques were employed to characterize the morphology and properties of the obtained carbon dots. The Gd/Ru-CDs are high mono-dispersity, uniform spherical nanoparticles with an average diameter of 4.2 nm. Moreover, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR) confirmed the composition and surface properties of the carbon dots. In particular, the successful doping of Gd/Ru enables the carbon dots not only show considerable magnetic resonance imaging (MRI) performance but also obtain better fluorescence (FL) properties, especially in the red emission area. More impressively, it has low cytotoxicity, excellent biocompatibility, and efficient reactive oxygen species (ROS) generation ability, making it an effective imaging-guided tumor treatment reagent. In vivo experiments have revealed that Gd/Ru-CDs can achieve light-induced tumor suppression and non-invasive fluorescence/magnetic resonance bimodal imaging reagents to monitor the treatment process of mouse tumor models. Thus, this simple and efficient carbon dot manufacturing strategy by doping functional metals has expanded avenues for the development and application of multifunctional all-in-one theranostics.
Cancer metastasis is the most important cause of cancer-related death, and epithelial-to-mesenchymal transition (EMT) plays crucial roles in cancer metastasis. Cordycepin (CD) is highly enriched in ...the medicinally used
Cordyceps
mushroom. In this study, we conducted the antimetastatic activities of CD, specifically focusing on its regulatory effects on EMT-inducing transcription factors (EMT-TFs) in triple-negative breast cancer (TNBC). Our study showed CD to inhibit the growth, migration, and invasion of BT549 and 4T1 cancer cell lines, by employing cell viability assay and real-time cell analyses. The protein levels of N-Cadherin and E-Cadherin, as well as their transcription factors TWIST1, SLUG, SNAIL1, and ZEB1 in BT549 and 4T1 cells, were estimated by Western blot assays. Results from dual-luciferase reporter assays demonstrated that CD is capable of inactivating the EMT signaling pathway by inhibiting TWIST1 and SLUG expression. Furthermore,
in vivo
studies with mice carrying cancer cell-derived allograft tumors showed the inhibitory effect of CD on cancer cell growth and metastasis. Furthermore, the additive/synergistic anti-metastasis effect of CD and thymoquinone (TQ), another natural product with promising anticancer roles, was demonstrated by combinational treatment. The results from this research indicate that CD would be a promising therapeutic molecule against TNBC by targeting EMT-TFs, possibly in SLUG, TWIST1, SNAIL1, and ZEB1.
The Chinese Imaging Genetics (CHIMGEN) study establishes the largest Chinese neuroimaging genetics cohort and aims to identify genetic and environmental factors and their interactions that are ...associated with neuroimaging and behavioral phenotypes. This study prospectively collected genomic, neuroimaging, environmental, and behavioral data from more than 7000 healthy Chinese Han participants aged 18-30 years. As a pioneer of large-sample neuroimaging genetics cohorts of non-Caucasian populations, this cohort can provide new insights into ethnic differences in genetic-neuroimaging associations by being compared with Caucasian cohorts. In addition to micro-environmental measurements, this study also collects hundreds of quantitative macro-environmental measurements from remote sensing and national survey databases based on the locations of each participant from birth to present, which will facilitate discoveries of new environmental factors associated with neuroimaging phenotypes. With lifespan environmental measurements, this study can also provide insights on the macro-environmental exposures that affect the human brain as well as their timing and mechanisms of action.
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