Ecotoxicological risk assessment of the novel psychoactive substance Esketamine: Emphasis on fish skeletal, behavioral, and vascular development.

Novel psychoactive substances (NPS), such as Esketamine (Esket), often contaminate the aquatic ecosystems following human consumption, raising concerns about the residues and potential ecological hazards to non-target organisms. The study used zebrafish as a model organism to investigate the developmental toxicity and ecotoxicological effects of acute Esket exposure. Our findings demonstrate that exposure to Esket significantly affected the early development and angiogenesis of zebrafish embryos/larvae. The mandible length was significantly decreased, and the angles between the pharyngeal arch cartilages were narrowed compared to the control group (all P < 0.05). Additionally, Esket resulted in a decrease of 47.6-89.8 % in the number of neural crest cells (NCC). Transcriptome analysis indicated altered expression of genes associated with cartilage and osteoblast growth. Moreover, Esket significantly inhibited swimming ability in zebrafish larvae and was accompanied by behavioral abnormalities and molecular alterations in the brain. Potential mechanisms underlying Esket-induced behavioral disorders involve neurotransmitter system impairment, abnormal cartilage development and function, aberrant vascular development, as well as perturbations in oxidative stress and apoptosis signaling pathways. Notably, the dysregulation of skeleton development through the bone morphogenetic protein (BMP) signaling pathway is identified as the primary mechanistic behind Esket-induced behavioral disorder. This study enhances our understanding of Esket's ecotoxicology profile and provides a comprehensive assessment of the environmental risks associated with NPS.

Visual toxicity in zebrafish larvae following exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), triphenyl phosphate (TPhP), and isopropyl phenyl diphenyl phosphate (IPPP).

TPhP and IPPP, alternatives to PBDEs as flame retardants, have been studied for their developmental toxicity, but their visual toxicities are less understood. In this study, zebrafish larvae were exploited to evaluate the potential ocular impairments following exposure to BDE-47, TPhP, and IPPP. The results revealed a range of ocular abnormalities, including malformation, vascular issues within the eyes, and histopathological changes in the retina. Notably, the visually mediated behavioral changes were primarily observed in IPPP and TPhP, indicating that they caused more severe eye malformations and vision impairment than BDE-47. Molecular docking and MD simulations showed stronger binding affinity of TPhP and IPPP to RAR and RBP receptors. Elevated ROS and T3 levels induced by these compounds led to apoptosis in larvae eyes, and increased GABA levels induced by TPhP and IPPP hindered retinal repair. In summary, our results indicate TPhP and IPPP exhibit severer visual toxicity than BDE-47, affecting eye development and visually guided behaviors. The underlying mechanism involves disruptions in RA signaling, retinal neurotransmitters imbalance, thyroid hormones up-regulation, and apoptosis in larvae eyes. This work highlights novel insights into the need for cautious use of these flame retardants due to their potential biological hazards, thereby offering valuable guidance for their safer applications.

miR-194-3p regulates epithelial-mesenchymal transition in embryonic epicardial cells via p120/ß-catenin signaling.

The epicardium is integral to cardiac development and facilitates endogenous heart regeneration and repair. While miR-194-3p is associated with cellular migration and invasion, its impact on epicardial cells remains uncharted. In this work we use gain-of-function and loss-of-function methodologies to investigate the function of miR-194-3p in cardiac development. We culture embryonic epicardial cells in vitro and subject them to transforming growth factor ß (TGF-ß) treatment to induce epithelial-mesenchymal transition (EMT) and monitor miR-194-3p expression. In addition, the effects of miR-194-3p mimics and inhibitors on epicardial cell development and changes in EMT are investigated. To validate the binding targets of miR-194-3p and its ability to recover the target gene-phenotype, we produce a mutant vector p120-catenin-3'UTR-MUT. In epicardial cells, TGF-ß-induced EMT results in a notable overexpression of miR-194-3p. The administration of miR-194-3p mimics promotes EMT, which is correlated with elevated levels of mesenchymal markers. Conversely, miR-194-3p inhibitor attenuates EMT. Further investigations reveal a negative correlation between miR-194-3p and p120-catenin, which influences ß-catenin level in the cell adhesion pathway. The suppression of EMT caused by the miR-194-3p inhibitor is balanced by silencing of p120-catenin. In conclusion, miR-194-3p directly targets p120-catenin and modulates its expression, which in turn alters ß-catenin expression, critically influencing the EMT process in the embryonic epicardial cells via the cell adhesion mechanism.

Simultaneous brain and neck time-of-flight MRA using spiral multiband with localized quadratic encoding.

PURPOSE: To develop a method that achieves simultaneous brain and neck time-of-flight (ToF) magnetic resonance angiography (MRA) within feasible scan timeframes. METHODS: Localized quadratic (LQ) encoding is efficient for both signal-to-noise ratio (SNR) and in-flow enhancement. We proposed a spiral multiband LQ method to enable simultaneous intracranial and carotid ToF-MRA within a single scan. To address the venous signal contamination that becomes a challenge with multiband (MB) ToF, tilt-optimized non-saturated excitation (TONE) and partial-Fourier slice selection (PFSS) were further introduced in the LQ framework to mitigate the venous signal and improve artery contrast. A sequential spiral MB and LQ reconstruction pipeline was employed to obtain the brain-and-neck image volumes. RESULTS: The proposed MB method was able to achieve simultaneous brain and neck ToF-MRA within a 2:50-min scan. The complementarily boosted SNR-efficiency by MB and LQ acquisitions allows for the increased spatial coverage without increase in scan time or noticeable compromise in SNR. The incorporation of both TONE and PFSS effectively alleviated the venous contamination with improved small vessel sensitivity. Selection of scan parameters such as the LQ factor and flip angle reflected the trade-off among SNR, blood contrast, and venous suppression. CONCLUSIONS: A novel MB spiral LQ approach was proposed to enable fast intracranial and carotid ToF-MRA with minimized venous corruption. The method has shown promise in MRA applications where large spatial coverage is necessary.

A 3D dual-echo spiral sequence for simultaneous dynamic susceptibility contrast and dynamic contrast-enhanced MRI with single bolus injection.

PURPOSE: Perfusion MRI reveals important tumor physiological and pathophysiologic information, making it a critical component in managing brain tumor patients. This study aimed to develop a dual-echo 3D spiral technique with a single-bolus scheme to simultaneously acquire both dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) data and overcome the limitations of current EPI-based techniques. METHODS: A 3D spiral-based technique with dual-echo acquisition was implemented and optimized on a 3T MRI scanner with a spiral staircase trajectory and through-plane SENSE acceleration for improved speed and image quality, in-plane variable-density undersampling combined with a sliding-window acquisition and reconstruction approach for increased speed, and an advanced iterative deblurring algorithm. Four volunteers were scanned and compared with the standard of care (SOC) single-echo EPI and a dual-echo EPI technique. Two patients were scanned with the spiral technique during a preload bolus and compared with the SOC single-echo EPI collected during the second bolus injection. RESULTS: Volunteer data demonstrated that the spiral technique achieved high image quality, reduced geometric artifacts, and high temporal SNR compared with both single-echo and dual-echo EPI. Patient perfusion data showed that the spiral acquisition achieved accurate DSC quantification comparable to SOC single-echo dual-dose EPI, with the additional DCE information. CONCLUSION: A 3D dual-echo spiral technique was developed to simultaneously acquire both DSC and DCE data in a single-bolus injection with reduced contrast use. Preliminary volunteer and patient data demonstrated increased temporal SNR, reduced geometric artifacts, and accurate perfusion quantification, suggesting a competitive alternative to SOC-EPI techniques for brain perfusion MRI.

Accelerating spiral deblurring with square kernels and low-pass preconditioning.

PURPOSE: Robust implementation of spiral imaging requires efficient deblurring. A deblurring method was previously proposed to separate and deblur water and fat simultaneously, based on image-space kernel operations. The goal of this work is to improve the performance of the previous deblurring method using kernels with better properties. METHODS: Four types of kernels were formed using different models for the region outside the collected k-space as well as low-pass preconditioning (LP). The performances of the kernels were tested and compared with both phantom and volunteer data. Data were also synthesized to evaluate the SNR. RESULTS: The proposed "square" kernels are much more compact than the previously used circular kernels. Square kernels have better properties in terms of normalized RMS error, structural similarity index measure, and SNR. The square kernels created by LP demonstrated the best performance of artifact mitigation on phantom data. CONCLUSIONS: The sizes of the blurring kernels and thus the computational cost can be reduced by the proposed square kernels instead of the previous circular ones. Using LP may further enhance the performance.

Volumetric T2 -weighted spin echo imaging with improved SNR using localized quadratic encoding and a spiral readout trajectory.

PURPOSE: To demonstrate T2 -weighted (single-echo) spin-echo (SE) imaging with near-optimal acquisition efficiency by applying SNR-efficient RF slice encoding and spiral readout. METHODS: A quadratic-phase (frequency swept) excitation RF pulse replaced the conventional excitation in T2 -weighted SE sequence to excite a thick slab that is internally spatially encoded by a variable phase along the slice direction. Highly overlapping slabs centered at every desired slice location were acquired in multiple passes, such that the entire imaging volume was excited by contiguous slabs in any given pass. Following 90° excitation, each slab was refocused with a conventional 180° RF to produce a SE signal, followed by a spiral in-out readout. A noise-insensitive reconstruction removed the quadratic phase in the spatial frequency domain, yielding desired slice resolution and improved SNR. RESULTS: Increasing the RF frequency sweep (hence, excitation width) allowed more frequent encoding of each slice over the multiple passes, improving final image SNR, until crosstalk ensued at excessive slab widths compared to their center-to-center spacing. With an optimized slab width, the proposed technique used all passes to acquire every prescribed slice, with substantially improved SNR over conventional SE or 2D-turbo-spin-echo (TSE) scans. Quantitative SNR measurements indicated similar SNR as 3D-TSE, but radiologist scoring favored 3D-TSE, mainly because of spiral-related artifacts and possibly because of regularized reconstructions in 3D-TSE. CONCLUSION: Using SNR-efficient slice excitation scheme and spiral readout helped eliminate SNR and temporal inefficiencies in conventional T2 -weighted imaging, yielding SNR independent of TR or number of passes.

Spiral inflow MRA with sliding-slice localized quadratic encoding.

PURPOSE: This work proposes a 2D/3D hybrid inflow MRA technique for fast scanning and high SNR and contrast-to-noise (CNR) efficiencies. METHODS: Localized quadratic (LQ) encoding was combined with a sliding-slice spiral acquisition. Inflow MRAs around the circle of Willis and the carotid bifurcations were collected on four healthy volunteers. Spiral images were deblurred without or with water-fat separation for sliding-slice LQ (ssLQ) out-of-phase (OP) and Dixon inflow MRAs, respectively. Results were compared to multiple overlapping thin slab acquisitions (MOTSA) and 2D OP inflow MRAs. Noise data were also acquired with RF and gradients turned off to compute maps of SNR and SNR efficiency. Quantitative assessment of relative contrast, CNR, and CNR efficiency for flow were performed in regions of interest. RESULTS: The sliding-slice spiral technique alone reduces scan time by 10% to 40% compared with a standard spiral acquisition scheme. The proposed spiral ssLQ OP achieves 50% higher scan speed than the spiral MOTSA with comparable SNR and CNR efficiencies, which are ∼100% higher than the Cartesian MOTSA for intracranial inflow MRAs. Spiral ssLQ Dixon inflow MRA provides better visibility for vessels around the fat compared to spiral ssLQ OP inflow MRA, with a trade-off of scan speed. Spiral ssLQ MRA with thinner slice thickness is two to five times faster than the 2D Cartesian inflow neck MRA around the carotid bifurcations, while also achieving higher SNR efficiency. CONCLUSION: The proposed spiral ssLQ is a fast and flexible MRA method with improved SNR and CNR efficiencies over traditional Cartesian inflow MRAs.

Evaluating efficient SENSE algorithms to deblur spiral MRI with fat/water separation.

PURPOSE: The combination of SENSE and spiral imaging with fat/water separation enables high temporal efficiency. However, the corresponding computation increases due to the blurring/deblurring operation across the multi-channel data. This study presents two alternative models to simplify computational complexity in the original full model (model 1). The performances of the models are evaluated in terms of the computation time and reconstruction error. METHODS: Two approximated spiral MRI reconstruction models were proposed: the comprehensive blurring before coil operation (model 2) and the regional blurring before coil operation (model 3), respectively, by altering the order of coil-sensitivity encoding process to distribute signals among the multi-channel coils. Four subjects were recruited for scanning both fully sampled T1 - and T2 -weighted brain image data with simulated undersampling for testing the computational efficiency and accuracy on the approximation models. RESULTS: Based on the examples, the computation time can be reduced to 31%-47% using model 2, and to 39%-56% using model 3. The quality of the water image remains unchanged among the three models, whereas the primary difference in image quality is in the fat channel. The fat images from model 3 are consistent with those from model 1, but those from model 2 have higher normalized error, differing by up to 4.8%. CONCLUSION: Model 2 provides the fastest computation but exhibits higher error in the fat channel, particularly in the high field and with long acquisition window. Model 3, an abridged alternative, is also faster than the full model and can maintain high accuracy in reconstruction.

A field map updating algorithm to improve fat-water spiral imaging.

PURPOSE: An accurate field map is essential to separate fat and water signals in a dual-echo chemical shift encoded spiral MRI scan. A rapid low-resolution B0 map prescan is usually performed before each exam. Occasional inaccuracy in these field map estimates can lead to misclassification of the water and fat signals as well as blurring artifacts in the reconstruction. The present work proposes a self-consistent model to evaluate residual field offsets according to the image data to improve the reconstruction quality and facilitate the scan efficiency. THEORY AND METHODS: The proposed method compares the phase differences of the two-echo data after correcting for fat frequency offsets. A more accurate field map is approximated according to the phase discrepancies and improved image quality. Experiments were conducted with simulated off-resonance on a numerical phantom, five volunteer head scans, and four volunteer abdominal scans for validation. RESULTS: The initial reconstruction of the demonstrated examples exhibit blurring artifacts and misregistration of fat and water because of the inaccuracy of the field map. The proposed method updates the field map to amend the fat and water estimation and improve image quality. CONCLUSIONS: This work presents a model to improve the quality of fat-water imaging of the spiral MRI by estimating a better field map from the acquired data. It allows reducing the field map pre-scans before each spiral scan under normal circumstances to increase scan efficiency.

High SNR rapid T1 -weighted MPRAGE using spiral imaging with long readouts and improved deblurring.

PURPOSE: The goal of this work is to present the implementation of 3D spiral high-resolution MPRAGE and to demonstrate that SNR and scan efficiency increase with the increment of readout time. THEORY: Simplified signal equations for MPRAGE indicate that the T1 contrast can be kept approximately the same by a simple relationship between the flip angle and the TR. Furthermore, if T1 contrast remains the same, image SNR depends on the square root of the product of the total scan time and the readout time. METHODS: MPRAGE spiral sequences were implemented with distributed spirals and spiral staircase on 3 Tesla scanners. Brain images of three volunteers were acquired with different readout times. Spiral images were processed with a joint water-fat separation and deblurring algorithm and compared to Cartesian images. Pure noise data sets were also acquired for SNR evaluation. RESULTS: Consistent T1 weighting can be achieved with various spiral readout lengths, and between spiral MPRAGE imaging and the traditional Cartesian MPRAGE imaging. Noise performance analysis demonstrates higher SNR efficiency of spiral MPRAGE imaging with matched T1 contrast compared to the Cartesian reference imaging. CONCLUSION: Fast, high SNR MPRAGE imaging is feasible with long readout spiral trajectories.

Transcription factor Foxp1 stimulates angiogenesis in adult rats after myocardial infarction.

Forkhead box protein P1 (FoxP1) is essential for cardiac development and the regulation of neovascularization, but its potential for cardiac angiogenesis has not been explored. This study aims to investigate the angiogenic role of FoxP1 in a rat model of myocardial infarction (MI). Adult male rats were subjected to MI, and Foxp1 was knocked down with lentivirus FoxP1 siRNA. Endothelial cell proliferation, angiogenesis, and cardiac function were also assessed. Cell scratch assay and tubule formation analysis were used to detect the migration ability and tube formation ability of human umbilical vein endothelial cells (HUVECs). Compared with that in the sham group, results showed that the expression of FoxP1 was significantly increased in the MI group. Foxp1 knockdown decreases FoxP1 expression, reduces angiogenesis, and increases collagen deposition. When Foxp1 was knocked down in HUVECs using FoxP1 siRNA lentivirus, cell proliferation, migration, and tube formation abilities decreased significantly. Our study showed that FoxP1 elicits pleiotropic beneficial actions on angiogenesis in the post-MI heart by promoting the proliferation of endothelial cells. FoxP1 should be considered a candidate for therapeutic cardiac angiogenesis.

Identification of key genes and mechanisms of epicardial adipose tissue in patients with diabetes through bioinformatic analysis.

Background: In recent years, peri-organ fat has emerged as a diagnostic and therapeutic target in metabolic diseases, including diabetes mellitus. Here, we performed a comprehensive analysis of epicardial adipose tissue (EAT) transcriptome expression differences between diabetic and non-diabetic participants and explored the possible mechanisms using various bioinformatic tools. Methods: RNA-seq datasets GSE108971 and GSE179455 for EAT between diabetic and non-diabetic patients were obtained from the public functional genomics database Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified using the R package DESeq2, then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed. Next, a PPI (protein-protein interaction) network was constructed, and hub genes were mined using STRING and Cytoscape. Additionally, CIBERSORT was used to analyze the immune cell infiltration, and key transcription factors were predicted based on ChEA3. Results: By comparing EAT samples between diabetic and non-diabetic patients, a total of 238 DEGs were identified, including 161 upregulated genes and 77 downregulated genes. A total of 10 genes (IL-1ß, CD274, PDCD1, ITGAX, PRDM1, LAG3, TNFRSF18, CCL20, IL1RN, and SPP1) were selected as hub genes. GO and KEGG analysis showed that DEGs were mainly enriched in the inflammatory response and cytokine activity. Immune cell infiltration analysis indicated that macrophage M2 and T cells CD4 memory resting accounted for the largest proportion of these immune cells. CSRNP1, RELB, NFKB2, SNAI1, and FOSB were detected as potential transcription factors. Conclusion: Comprehensive bioinformatic analysis was used to compare the difference in EAT between diabetic and non-diabetic patients. Several hub genes, transcription factors, and immune cell infiltration were identified. Diabetic EAT is significantly different in the inflammatory response and cytokine activity. These findings may provide new targets for the diagnosis and treatment of diabetes, as well as reduce potential cardiovascular complications in diabetic patients through EAT modification.

Protein arginine methyltransferase PRMT1 promotes adipogenesis by modulating transcription factors C/EBPß and PPARγ.

Protein arginine methyltransferase 1 (PRMT1) methylates a variety of histone and nonhistone protein substrates to regulate multiple cellular functions such as transcription, DNA damage response, and signal transduction. It has been reported as an emerging regulator of various metabolic pathways including glucose metabolism in the liver, atrophy in the skeletal muscle, and lipid catabolism in the adipose tissue. However, the underlying mechanisms governing how PRMT1 regulates adipogenesis remain elusive. Here, we delineate the roles of PRMT1 in mitotic clonal expansion and adipocyte differentiation. Gain and loss of functions demonstrate that PRMT1 is essential for adipogenesis of 3T3-L1 and C3H10T1/2 cells. Mechanistically, we show PRMT1 promotes the expression of transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) by catalyzing histone modification H4R3me2a and impedes the activation of Wnt/ß-catenin signaling by increasing the level of Axin to accelerate adipogenic differentiation. In addition, we demonstrate mitotic clonal expansion is suppressed by PRMT1 deficiency. PRMT1 interacts with transcription factor CCATT enhancer-binding protein ß (C/EBPß), and the absence of PRMT1 leads to the depressed phosphorylation of C/EBPß. Interestingly, we discover PRMT1 acts as a positive regulator of C/EBPß protein stability through decreasing the level of E3 ubiquitin ligase Smurf2, which promotes the ubiquitination and degradation of C/EBPß, thus facilitating adipogenesis. Collectively, these discoveries highlight a critical role of PRMT1 in adipogenesis and provide potential therapeutic targets for the treatment of obesity.

A Fluorescent Linear Conjugated Polymer Constructed from Pillararene and Anthracene.

Over the past few years, conjugated polymers (CPs) have aroused much attention owing to their rigid conjugated structures, which can perform well in light harvesting and energy transfer and offer great potential in materials chemistry. In this article, we fabricate a new luminescent linear CP p(P[5](OTf)2-co-9,10-dea) via the Sonogashira coupling of 9,10-diethynylanthracene and trifluoromethanesulfonic anhydride (OTf) modified pillar[5]arene, generating enhanced yellow-green fluorescence emission at around 552 nm. The reaction condition was screened to get a deeper understanding of this polymerization approach, resulting in an excellent yield as high as 92% ultimately. Besides the optical properties, self-assembly behaviors of the CP in low/high concentrations were studied, where interesting adjustable morphologies from tube to sheet were observed. In addition, the fluorescence performance and structural architecture can be disturbed by the host-guest reorganization between the host CP and the guest adiponitrile, suggesting great potential of this CP material in the field of sensing and detection.

Predicting the Key Genes Involved in Aortic Valve Calcification Through Integrated Bioinformatics Analysis.

Background: Valvular heart disease is obtaining growing attention in the cardiovascular field and it is believed that calcific aortic valve disease (CAVD) is the most common valvular heart disease (VHD) in the world. CAVD does not have a fully effective treatment to delay its progression and the specific molecular mechanism of aortic valve calcification remains unclear. Materials and Methods: We obtained the gene expression datasets GSE12644 and GSE51472 from the public comprehensive free database GEO. Then, a series of bioinformatics methods, such as GO and KEGG analysis, STING online tool, Cytoscape software, were used to identify differentially expressed genes in CAVD and healthy controls, construct a PPI network, and then identify key genes. In addition, immune infiltration analysis was used via CIBERSORT to observe the expression of various immune cells in CAVD. Results: A total of 144 differential expression genes were identified in the CAVD samples in comparison with the control samples, including 49 up-regulated genes and 95 down-regulated genes. GO analysis of DEGs were most observably enriched in the immune response, signal transduction, inflammatory response, proteolysis, innate immune response, and apoptotic process. The KEGG analysis revealed that the enrichment of DEGs in CAVD were remarkably observed in the chemokine signaling pathway, cytokine-cytokine receptor interaction, and PI3K-Akt signaling pathway. Chemokines CXCL13, CCL19, CCL8, CXCL8, CXCL16, MMP9, CCL18, CXCL5, VCAM1, and PPBP were identified as the hub genes of CAVD. It was macrophages that accounted for the maximal proportion among these immune cells. The expression of macrophages M0, B cells memory, and Plasma cells were higher in the CAVD valves than in healthy valves, however, the expression of B cells naïve, NK cells activated, and macrophages M2 were lower. Conclusion: We detected that chemokines CXCL13, CXCL8, CXCL16, and CXCL5, and CCL19, CCL8, and CCL18 are the most important markers of aortic valve disease. The regulatory macrophages M0, plasma cells, B cells memory, B cells naïve, NK cells activated, and macrophages M2 are probably related to the occurrence and the advancement of aortic valve stenosis. These identified chemokines and these immune cells may interact with a subtle adjustment relationship in the development of calcification in CAVD.

Inhibition of Notch Signaling Promotes the Differentiation of Epicardial Progenitor Cells into Adipocytes.

BACKGROUND: The role of Notch signaling pathway in the differentiation of epicardial progenitor cells (EPCs) into adipocytes is unclear. The objective is to investigate the effects of Notch signaling on the differentiation of EPCs into adipocytes. METHODS: Frozen sections of C57BL/6J mouse hearts were used to observe epicardial adipose tissue (EAT), and genetic lineage methods were used to trace EPCs. EPCs were cultured in adipogenic induction medium with Notch ligand jagged-1 or γ-secretase inhibitor DAPT. The adipocyte markers, Notch signaling, and adipogenesis transcription factors were determined. RESULTS: There was EAT located at the atrial-ventricular groove in mouse. By using genetic lineage tracing methods, we found that EPCs were a source of epicardial adipocytes. EPCs had lipid droplet accumulation, and the expression of adipocyte markers FABP-4 and perilipin-1 was upregulated under adipogenic induction. Activating the Notch signaling with jagged-1 attenuated the adipogenic differentiation of EPCs and downregulated the key adipogenesis transcription factor peroxisome proliferator activated receptor-γ (PPAR-γ), while inhibiting the signaling promoted adipogenic differentiation and upregulated PPAR-γ. When blocking PPAR-γ, the role of Notch signaling in promoting adipogenic differentiation was inhibited. CONCLUSIONS: EPCs are a source of epicardial adipocytes. Downregulation of the Notch signaling pathway promotes the differentiation of EPCs into adipocytes via PPAR-γ.

Investigation of the underlying genes and mechanism of familial hypercholesterolemia through bioinformatics analysis.

BACKGROUND: Familial hypercholesterolemia (FH) is one of the commonest inherited metabolic disorders. Abnormally high level of low-density lipoprotein cholesterol (LDL-C) in blood leads to premature atherosclerosis onset and a high risk of cardiovascular disease (CVD). However, the specific mechanisms of the progression process are still unclear. Our study aimed to investigate the potential differently expressed genes (DEGs) and mechanism of FH using various bioinformatic tools. METHODS: GSE13985 and GSE6054 were downloaded from the Gene Expression Omnibus (GEO) database for bioinformatic analysis in this study. First, limma package of R was used to identify DEGs between blood samples of patients with FH and those from healthy individuals. Then, the functional annotation of DEGs was carried out by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) analysis. Based on Search Tool for the Retrieval of Interacting Genes (STRING) tool, we constructed the Protein-Protein Interactions (PPIs) network among DEGs and mined the core genes as well. RESULTS: A total of 102 communal DEGs (49 up-regulated and 53 down-regulated) are identified in FH samples compared with control samples. The functional changes of DEGs are mainly associated with the focal adhere and glucagon signaling pathway. Ten genes (ITGAL, TLN1, POLR2A, CD69, GZMA, VASP, HNRNPUL1, SF1, SRRM2, ITGAV) were identified as core genes. Bioinformatic analysis showed that the core genes are mainly enriched in numerous processes related to cell adhesion, integrin-mediated signaling pathway and cell-matrix adhesion. In the transcription factor (TF) target regulating network, 219 nodes were detected, including 214 DEGs and 5 TFs (SP1, EGR3, CREB, SEF1, HOX13). In conclusion, the DEGs and hub genes identified in this study may help us understand the potential etiology of the occurrence and development of AS. CONCLUSION: Up-regulated ITGAL, TLN1, POLR2A, VASP, HNRNPUL1, SF1, SRRM2, and down-regulated CD69, GZMA and ITGAV performed important promotional effects for the formation of atherosclerotic plaques those suffering from FH. Moreover, SP1, EGR3, CREB, SEF1 and HOX13 were the potential transcription factors for DEGs and could serve as underlying targets for AS rupture prevention. These findings provide a theoretical basis for us to understand the potential etiology of the occurrence and development of AS in FH patients and we may be able to find potential diagnostic and therapeutic targets.

Controlled aliasing for improved parallel imaging with a 3D spiral staircase trajectory.

PURPOSE: To introduce a modified 3D stack-of-spirals trajectory and efficient SENSE reconstruction for improved through-plane undersampling, while maintaining SNR efficiency and other benefits of spiral acquisitions. METHODS: A novel spiral staircase trajectory is introduced. This trajectory is a modified stack of spirals, in which spiral arms are distributed between partitions along kz . The trajectory maintains the efficient separable reconstruction with a Cartesian fast Fourier transform along the kz direction, followed by a 2D slice-by-slice gridding reconstruction. An additional intermediate step introduces a phase correction to collapse the spiral arms into the prescribed slice planes. For data undersampled through plane, this produces aliasing with reduced coherence, controlled by the arm-ordering. Undersampled data can then be reconstructed with reduced g-factor using a conjugate gradient-based iterative SENSE algorithm. RESULTS: The trajectory significantly improves g-factor for through-plane accelerated acquisitions. Improvement manifests through both reduced overall g-factor and reduced structure in the g-factor maps. In the presented experiments, the mean g-factor decreased from 1.26 to 0.93 and the maximum g-factor decreased from 3.89 to 1.15 for R = 2 spiral staircase when compared with stack of spirals, and the mean g-factor decreased from 2.51 to 0.94 and the maximum g-factor decreased from 8.26 to 1.35 for R = 3 spiral staircase when compared with stack of spirals. CONCLUSION: The novel spiral staircase trajectory offers improved aliasing characteristics for through-plane parallel imaging acceleration in 3D spiral acquisitions.

Correction of B0 eddy current effects in spiral MRI.

PURPOSE: B0 eddy currents are a subtle but important source of artifacts in spiral MRI. This study illustrates the importance of addressing these artifacts and presents a system response-based eddy current correction strategy using B0 eddy current phase measurements on a phantom. METHODS: B0 and linear eddy current system response measurements were estimated from phantom-based measurement and used to predict residual eddy current effects in spiral acquisitions. The measurements were evaluated across multiple systems and gradient sets. The corresponding eddy current corrections were studied in both axial spiral-in/out TSE and sagittal spiral-out MPRAGE volunteer data. RESULTS: Correction of B0 eddy currents using the proposed method mitigated blurriness in the axial spiral-in/out images and artifacts in the sagittal spiral-out images. The system response measurement was found to yield repeatable results over time with some variation in the B0 eddy current responses measured between different systems. CONCLUSIONS: The proposed eddy current correction framework was effective in mitigating the effects of residual B0 and linear eddy currents. Any spiral acquisition should take residual eddy currents into account. This is particularly important in spiral-in/out acquisitions.