Exploring Imaging Genetic Markers of Alzheimer's Disease Based on a Novel Nonlinear Correlation Analysis Algorithm.

Alzheimer's disease (AD) is an irreversible neurological disorder characterized by insidious onset. Identifying potential markers in its emergence and progression is crucial for early diagnosis and treatment. Imaging genetics typically merges genetic variables with multiple imaging parameters, employing various association analysis algorithms to investigate the links between pathological phenotypes and genetic variations, and to unearth molecular-level insights from brain images. However, most existing imaging genetics algorithms based on sparse learning assume a linear relationship between genetic factors and brain functions, limiting their ability to discern complex nonlinear correlation patterns and resulting in reduced accuracy. To address these issues, we propose a novel nonlinear imaging genetic association analysis method, Deep Self-Reconstruction-based Adaptive Sparse Multi-view Deep Generalized Canonical Correlation Analysis (DSR-AdaSMDGCCA). This approach facilitates joint learning of the nonlinear relationships between pathological phenotypes and genetic variations by integrating three different types of data: structural magnetic resonance imaging (sMRI), single-nucleotide polymorphism (SNP), and gene expression data. By incorporating nonlinear transformations in DGCCA, our model effectively uncovers nonlinear associations across multiple data types. Additionally, the DSR algorithm clusters samples with identical labels, incorporating label information into the nonlinear feature extraction process and thus enhancing the performance of association analysis. The application of the DSR-AdaSMDGCCA algorithm on real data sets identified several AD risk regions (such as the hippocampus, parahippocampus, and fusiform gyrus) and risk genes (including VSIG4, NEDD4L, and PINK1), achieving maximum classification accuracy with the fewest selected features compared to baseline algorithms. Molecular biology enrichment analysis revealed that the pathways enriched by these top genes are intimately linked to AD progression, affirming that our algorithm not only improves correlation analysis performance but also identifies biologically significant markers.

Palladium-Catalyzed Cross-Coupling of gem-Difluorocyclopropanes with gem-Diborylalkanes for the Synthesis of Boryl-Substituted Fluorinated Alkenes.

This study presents a novel method for the regioselective coupling of gem-difluorinated cyclopropanes with gem-diborylmethane, utilizing a Pd-catalyst system. This innovative approach enables the synthesis of 2-fluoroalkenyl monoboronate scaffolds with high Z-selectivity. The resulting products undergo further transformations, including oxidation, Suzuki cross-coupling, and trifluoroborylation, all of which are achieved with good yields. This work introduces a valuable synthetic pathway to access important fluorinated compounds for various applications in organic chemistry.

Gelidocalamusalbozonatus (Poaceae, Bambusoideae), a new species from the southeast of Chongqing, China, and analysis of the morphological diversity in the core group of Gelidocalamus.

Gelidocalamusalbozonatus W. G. Zhang, S. R. Yi & Y. L. Li, a new species of Gelidocalamus, collected from Pengshui County of Chongqing City in China, was described and illustrated herein. In this study, key morphological characters were compared between the new species and other eight "gelido-" members of Gelidocalamus. By using scanning electron microscopy (SEM), its leaf epidermal characters were observed in comparison with those of another three Gelidocalamus representatives. Our results show that the new taxon has the typical characteristics of the genus Gelidocalamus, both macromorphologically and micromorphologically. Moreover, it was most similar to G.tessellatus, but differed by a ring of white tomenta below per node, culm sheath base with densely purple verrucous setae and foliage leaf blades mesophyll.

[Expression and clinical significance of plasma exosomal miR-34-5p and miR-142-3p in systemic sclerosis].

OBJECTIVE: To detect the expression of plasma exosomal microRNA (miRNA) in systemic sclerosis (SSc), and to investigate its clinical significance. METHODS: A total of 20 patients who were initially diagnosed with SSc and did not receive medication in Department of Rheumatology and Immunology of Meizhou People' s Hospital from January 2020 to January 2022 were recruited, as well as 15 healthy individuals whose gender and age matched with those of the SSc patients. Plasma exosomes were isolated using ultracentrifugation method. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were detected by quantative real-time polymerase chain reaction (qRT-PCR). Correlations between the expression levels of exosomal miRNAs and clinical characteristic were analyzed by Spearman's rank correlation coefficient test. RESULTS: The mean age of 20 patients with SSc was (52.6±12.6) years, including 7 males and 13 females. Among the 20 SSc patients, 13 cases were diagnosed as limited cutaneous systemic sclerosis (lcSSc) and 7 cases were diagnosed as diffuse cutaneous systemic sclerosis (dcSSc) according to the extent of skin involvement. According to the findings of high resolution chest CT, 7 of 20 SSc patients were diagnosed with interstitial lung disease (ILD) and 13 SSc patients were diagnosed with non-ILD. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were significantly elevated in the SSc patients compared with those in the healthy controls group (P=0.003, P=0.000 1, and P=0.016, respectively). Compared with the SSc patients without ILD, the expression levels of miR-34-5p and miR-142-3p were significantly lower in the SSc patients with ILD (P=0.037 and P=0.015, respectively). The expression levels of exosomal miR-34-5p and miR-142-3p showed negative correlation with ILD (r=-0.48, P=0.031 and r=-0.55, P=0.011, respectively), and arthritis (r=-0.46, P=0.040 and r=-0.48, P=0.032, respectively). The expression levels of exosomal miR-142-3p showed a negative correlation with erythrocyte sedimentation rate (ESR) (r=-0.55, P=0.012). CONCLUSION: Plasma exosomal miR-34-5p, miR-92-3p and miR-142-3p were dysregulated in SSc. The dyregulation of exosomal miR-34-5p and miR-142-3p showed correlation with SSc associated ILD (SSc-ILD).

Decellularized diseased tissues: current state-of-the-art and future directions.

Decellularized matrices derived from diseased tissues/organs have evolved in the most recent years, providing novel research perspectives for understanding disease occurrence and progression and providing accurate pseudo models for developing new disease treatments. Although decellularized matrix maintaining the native composition, ultrastructure, and biomechanical characteristics of extracellular matrix (ECM), alongside intact and perfusable vascular compartments, facilitates the construction of bioengineered organ explants in vitro and promotes angiogenesis and tissue/organ regeneration in vivo, the availability of healthy tissues and organs for the preparation of decellularized ECM materials is limited. In this paper, we review the research advancements in decellularized diseased matrices. Considering that current research focuses on the matrices derived from cancers and fibrotic organs (mainly fibrotic kidney, lungs, and liver), the pathological characterizations and the applications of these diseased matrices are mainly discussed. Additionally, a contrastive analysis between the decellularized diseased matrices and decellularized healthy matrices, along with the development in vitro 3D models, is discussed in this paper. And last, we have provided the challenges and future directions in this review. Deep and comprehensive research on decellularized diseased tissues and organs will promote in-depth exploration of source materials in tissue engineering field, thus providing new ideas for clinical transformation.

Karyotype and genome size variation in Delphinium subg. Anthriscifolium (Ranunculaceae).

Five taxa of Delphiniumsubg.Anthriscifolium have been karyologically studied through chromosome counting, chromosomal measurement, and karyotype symmetry. Each taxon that we investigated has a basic chromosome number of x = 8, D.anthriscifoliumvar.savatieri, D.anthriscifoliumvar.majus, D.ecalcaratum, and D.callichromum were diploid with 2n = 16, while D.anthriscifoliumvar.anthriscifolium was tetraploid with 2n = 32. Monoploid chromosome sets of the investigated diploid taxa contained 1 metacentric chromosome, 3 submetacentric chromosomes, and 4 subtelocentric chromosomes. Higher interchromosomal asymmetry (CVCL) was present in D.ecalcaratum and D.callichromum than in other taxa. The highest levels of intrachromosomal asymmetry (MCA) and heterogeneity in centromere position (CVCI) were found in D.anthriscifoliumvar.majus. Diploid and tetraploid genome sizes varied by 3.02-3.92 pg and 6.04-6.60 pg, respectively. Karyotype and genome size of D.anthriscifoliumvar.savatieri, D.anthriscifoliumvar.majus, D.callichromum, and D.ecalcaratum were reported for the first time. Finally, based on cytological and morphological data, the classification of Delphiniumanthriscifolium was revised.

Biomimetic hydrogel derived from decellularized dermal matrix facilitates skin wounds healing.

Cutaneous wound healing affecting millions of people worldwide represents an unsolvable clinical issue that is frequently challenged by scar formation with dramatical pain, impaired mobility and disfigurement. Herein, we prepared a kind of light-sensitive decellularized dermal extracellular matrix-derived hydrogel with fast gelling performance, biomimetic porous microstructure and abundant bioactive functions. On account of its excellent cell biocompatibility, this ECM-derived hydrogel could induce a marked cellular infiltration and enhance the tube formation of HUVECs. In vivo experiments based upon excisional wound splinting model showed that the hydrogel prominently imparted skin wound healing, as evidenced by notably increased skin appendages and well-organized collagen expression, coupled with significantly enhanced angiogenesis. Moreover, the skin regeneration mediated by this bioactive hydrogel was promoted by an accelerated M1-to-M2 macrophage phenotype transition. Consequently, the decellularized dermal matrix-derived bioactive hydrogel orchestrates the entire skin healing microenvironment to promote wound healing and will be of high value in treatment of cutaneous wound healing. As such, this biomimetic ddECMMA hydrogel provides a promising versatile opinion for the clinical translation.

Application of orthogonal sparse joint non-negative matrix factorization based on connectivity in Alzheimer's disease research.

Based on the mining of micro- and macro-relationships of genetic variation and brain imaging data, imaging genetics has been widely applied in the early diagnosis of Alzheimer's disease (AD). However, effective integration of prior knowledge remains a barrier to determining the biological mechanism of AD. This paper proposes a new connectivity-based orthogonal sparse joint non-negative matrix factorization (OSJNMF-C) method based on integrating the structural magnetic resonance image, single nucleotide polymorphism and gene expression data of AD patients; the correlation information, sparseness, orthogonal constraint and brain connectivity information between the brain image data and genetic data are designed as constraints in the proposed algorithm, which efficiently improved the accuracy and convergence through multiple iterative experiments. Compared with the competitive algorithm, OSJNMF-C has significantly smaller related errors and objective function values than the competitive algorithm, showing its good anti-noise performance. From the biological point of view, we have identified some biomarkers and statistically significant relationship pairs of AD/mild cognitive impairment (MCI), such as rs75277622 and BCL7A, which may affect the function and structure of multiple brain regions. These findings will promote the prediction of AD/MCI.

A Novel Longitudinal Phenotype-Genotype Association Study Based on Deep Feature Extraction and Hypergraph Models for Alzheimer's Disease.

Traditional image genetics primarily uses linear models to investigate the relationship between brain image data and genetic data for Alzheimer's disease (AD) and does not take into account the dynamic changes in brain phenotype and connectivity data across time between different brain areas. In this work, we proposed a novel method that combined Deep Subspace reconstruction with Hypergraph-Based Temporally-constrained Group Sparse Canonical Correlation Analysis (DS-HBTGSCCA) to discover the deep association between longitudinal phenotypes and genotypes. The proposed method made full use of dynamic high-order correlation between brain regions. In this method, the deep subspace reconstruction technique was applied to retrieve the nonlinear properties of the original data, and hypergraphs were used to mine the high-order correlation between two types of rebuilt data. The molecular biological analysis of the experimental findings demonstrated that our algorithm was capable of extracting more valuable time series correlation from the real data obtained by the AD neuroimaging program and finding AD biomarkers across multiple time points. Additionally, we used regression analysis to verify the close relationship between the extracted top brain areas and top genes and found the deep subspace reconstruction approach with a multi-layer neural network was helpful in enhancing clustering performance.

Recent advances in decellularized biomaterials for wound healing.

The skin is one of the most essential organs in the human body, interacting with the external environment and shielding the body from diseases and excessive water loss. Thus, the loss of the integrity of large portions of the skin due to injury and illness may lead to significant disabilities and even death. Decellularized biomaterials derived from the extracellular matrix of tissues and organs are natural biomaterials with large quantities of bioactive macromolecules and peptides, which possess excellent physical structures and sophisticated biomolecules, and thus, promote wound healing and skin regeneration. Here, we highlighted the applications of decellularized materials in wound repair. First, the wound-healing process was reviewed. Second, we elucidated the mechanisms of several extracellular matrix constitutes in facilitating wound healing. Third, the major categories of decellularized materials in the treatment of cutaneous wounds in numerous preclinical models and over decades of clinical practice were elaborated. Finally, we discussed the current hurdles in the field and anticipated the future challenges and novel avenues for research on decellularized biomaterials-based wound treatment.

An improved MOPSO approach with adaptive strategy for identifying biomarkers from gene expression dataset.

Biomarkers plays an important role in the prediction and diagnosis of cancers. Therefore, it is urgent to design effective methods to extract biomarkers. The corresponding pathway information of the microarray gene expression data can be obtained from public database, which makes possible to identify biomarkers based on pathway information and has been attracted extensive attention. In the most existing methods, all the member genes in the same pathway are regarded as equally important for inferring pathway activity. However, the contribution of each gene should be different in the process of inferring pathway activity. In this research, an improved multi-objective particle swarm optimization algorithm with penalty boundary intersection decomposition mechanism (IMOPSO-PBI) has been proposed to quantify the relevance of each gene in pathway activity inference. In the proposed algorithm, two optimization objectives namely t-score and z-score respectively has been introduced. In addition, in order to solve the problem that optimal set with poor diversity in the most multi-objective optimization algorithms, an adaptive mechanism for adjusting penalty parameters based on PBI decomposition has been introduced. The performance of the proposed IMOPSO-PBI approach compared with some existing methods on six gene expression datasets has been given. To verify the effectiveness of the proposed IMOPSO-PBI algorithm, experiments were carried out on six gene datasets and the results has been compared with the existing methods. The comparative experiment results show that the proposed IMOPSO-PBI method has a higher classification accuracy and the extracted feature genes are verified possess biological significance.

Gelidocalamuszixingensis (Poaceae, Bambusoideae, Arundinarieae), a new species from southern China revealed by morphological and molecular evidence.

The genus Gelidocalamus T. H. Wen, endemic to southern China, is a small but taxonomically problematic genus of Arundinarieae (Poaceae, Bambusoideae). During field work, a population of Gelidocalamus from Zixing, Hunan, was discovered, appearing to be distinct from our previously identified collection. Comparisons of the population of Zixing were performed by using scanning electron microscopy (SEM) and a plastid genome-based phylogeny. Morphologically, it was mostly similar to G.multifolius, but differed by culm leaf erect with densely white pubescence, apical branch sheath much longer than the internodes and foliage leaf larger. Phylogenetically, the new species was well-supported as a sister to the clade of G.multifolius + G.tessellatus, and the above three taxa were clustered in the Shibataea clade (IV) of Arundinarieae. Thus, the new species, formally named as Gelidocalamuszixingensis W.G.Zhang, G.Y.Yang & C.K.Wang, was described and illustrated herein.

Multimodal data fusion based on IGERNNC algorithm for detecting pathogenic brain regions and genes in Alzheimer's disease.

At present, the study on the pathogenesis of Alzheimer's disease (AD) by multimodal data fusion analysis has been attracted wide attention. It often has the problems of small sample size and high dimension with the multimodal medical data. In view of the characteristics of multimodal medical data, the existing genetic evolution random neural network cluster (GERNNC) model combine genetic evolution algorithm and neural network for the classification of AD patients and the extraction of pathogenic factors. However, the model does not take into account the non-linear relationship between brain regions and genes and the problem that the genetic evolution algorithm can fall into local optimal solutions, which leads to the overall performance of the model is not satisfactory. In order to solve the above two problems, this paper made some improvements on the construction of fusion features and genetic evolution algorithm in GERNNC model, and proposed an improved genetic evolution random neural network cluster (IGERNNC) model. The IGERNNC model uses mutual information correlation analysis method to combine resting-state functional magnetic resonance imaging data with single nucleotide polymorphism data for the construction of fusion features. Based on the traditional genetic evolution algorithm, elite retention strategy and large variation genetic algorithm are added to avoid the model falling into the local optimal solution. Through multiple independent experimental comparisons, the IGERNNC model can more effectively identify AD patients and extract relevant pathogenic factors, which is expected to become an effective tool in the field of AD research.

Triplanar osteotomy combined with proximal tibial transverse transport to accelerate healing of recalcitrant diabetic foot ulcers.

BACKGROUND: Management of recalcitrant diabetic foot ulcers remains challenging. Tibial transverse transport (TTT) is an effective method for enhancing the healing of foot ulcers. This retrospective study reports a novel triplanar osteotomy in the tibia and assesses the clinical outcomes of TTT for diabetic foot ulcers. METHODS: Fifty-nine patients with recalcitrant diabetic foot ulcers were divided into the TTT (32 patients) and control (27 patients) groups. In the TTT group, the patients underwent triplanar osteotomy of the proximal tibia, followed by 2 weeks of medial distraction and 2 weeks of lateral distraction. In the control group, the patients received conventional management, including debridement, revascularization, and reconstruction. Ulcer healing and healing time, amputation, recurrence, and complications were assessed at an 18-month follow-up visit. Computed tomography angiography (CTA) was used to evaluate vessel changes in the lower limbs of patients in the TTT group. RESULTS: The TTT group was superior to the control group in the healing rate (90.6% [29/32] vs. 66.7% [18/27]) and the healing time (4.6 ± 1.7 months vs. 7.4 ± 2.5 months), respectively. The proportions of amputation and recurrence in the TTT group were lower than that in the control group, without statistical difference. After triplanar osteotomy and transverse distraction, CTA demonstrated an increase in small vessels in the wound and ipsilateral limb. All patients achieved satisfactory union of the osteotomized bone fragment after removal of the external fixator. CONCLUSIONS: Triplanar osteotomy combined with proximal tibial transverse distraction accelerates wound healing and limb salvage caused by severe and recalcitrant diabetic foot ulcers. Triplanar osteotomy not only increases the bone contact area, which is beneficial for rapid bone reconstruction, but also preserves the vascularization of the bone fragment and substantially facilitates capillary angiogenesis during distraction. These results suggest that triplanar osteotomy followed by tibial transverse distraction is an effective method for treating diabetic foot ulcers.

Masquelet technique with radical debridement and alternative fixation in treatment of infected bone nonunion.

Background: Infected bone nonunion is the toughest problem in fracture-related infection, leading to high disability and recurrence. The aim of this study was to evaluate the effectiveness of the Masquelet technique with radical debridement and alternative fixation in the management of infected bone nonunion. Patients and Methods: A retrospective study of prospectively collected data in two trauma centers was performed from 2016 to 2020. Patients diagnosed as infected bone nonunion were included in this study. The initial implant was removed and all patients received a two-stage Masquelet procedure with radical debridement and alternative fixation. The disappearance of inflammatory manifestations and regression of infection indicators (such as interleukin-6 (IL-6), C-reactive protein, white blood cell count) to the normal range were regarded as radical debridement. The alternative fixation depended on local soft tissue conditions. Results were evaluated according to clinical and radiographic assessment and patient satisfaction. Results: A total of 23 patients were included in our study. Six of them received internal fixation, while the other 17 received external fixation. Of the 23 cases, 21 were successfully reconstructed without infection recurrence, except 2 reinfected cases. Mean full weight bearing time was 6.6 months follow-up post last surgery. Out of the 23, 20 cases had satisfactory functional outcomes without additional bone or soft tissue comorbidities. Discrepancies in leg length and joint stiffness were observed in three cases and marked as unsatisfied results. Conclusions: Infected bone nonunion can be successfully managed using the Masquelet technique under radical debridement combined with an alternative fixation method.

Biomarker Genes Discovery of Alzheimer's Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia.

Microglia, the major immune cells in the brain, mediate neuroinflammation, increased oxidative stress, and impaired neurotransmission in Alzheimer's disease (AD), in which most AD risk genes are highly expressed. In microglia, due to the limitations of current single-omics data analysis, risk genes, the regulatory mechanisms, the mechanisms of action of immune responses and the exploration of drug targets for AD immunotherapy are still unclear. Therefore, we proposed a method to integrate multi-omics data based on the construction of gene regulatory networks (GRN), by combining weighted gene co-expression network analysis (WGCNA) with single-cell regulatory network inference and clustering (SCENIC). This enables snRNA-seq data and bulkRNA-seq data to obtain data on the deeper intermolecular regulatory relationships, related genes, and the molecular mechanisms of immune-cell action. In our approach, not only were central transcription factors (TF) STAT3, CEBPB, SPI1, and regulatory mechanisms identified more accurately than with single-omics but also immunotherapy targeting central TFs to drugs was found to be significantly different between patients. Thus, in addition to providing new insights into the potential regulatory mechanisms and pathogenic genes of AD microglia, this approach can assist clinicians in making the most rational treatment plans for patients with different risks; it also has significant implications for identifying AD immunotherapy targets and targeting microglia-associated immune drugs.

Simultaneous reconstruction of septic composite defects in lower extremities: Combination of fasciocutaneous perforator flap and Masquelet technique.

Background: Management of composite defects with deep infection is a challenge to reconstructive surgeons. This study aimed to demonstrate the versatility, safety, and complications of simultaneous reconstruction of infectious composite defects with fasciocutaneous perforator flap combined with the Masquelet technique. Methods: This study presents 10 patients in whom a fasciocutaneous perforator flap combined with the Masquelet technique was used to restore soft tissue and bone defects of the lower extremity, and were admitted in two level 1 trauma centers in Shanghai. The first stage included debridement of necrotic bone and infected tissues, implantation of a polymethylmethacrylate cement spacer to cover the void; bridging fixation of the osseous defect using external or internal fixators, and soft-tissue reconstruction with a fasciocutaneous perforator flap. The second stage included cement spacer removal with membrane preservation, refreshing bone edges, and grafting the cavity with bone morphogenetic proteins and autologous iliac bone graft. Results: The mean follow-up duration after autologous bone graft was 17.5 months. The average bony defects and average flap dimensions were 7.1 cm and 44.9 cm2, respectively. All flaps survived uneventfully. No recurrence of infection was detected in either the second stage of surgery or follow-up period. The mean duration of bone consolidation was 31.9 weeks. One patient had a 2 cm leg length discrepancy, and one patient had mild foot drop. No residual deformity requiring a secondary procedure occurred. Conclusion: Fasciocutaneous perforator flap combined with Masquelet technique provides a reliable and versatile alternative for patients with composite defects resulting from lower extremity infection.

The Effects of Bone Cement Volume in Percutaneous Vertebroplasty for Thoracolumbar Junction Vertebral Compression Fractures: A Clinical Comparative Study.

We compared the outcomes of patients treated with different volumes of polymethyl methacrylate bone cement during percutaneous vertebroplasty (PVP) for thoracolumbar vertebral compression fractures. We performed a comparative, retrospective study of 316 patients who underwent PVP for a single-level thoracolumbar vertebral compression fracture. Patients were divided into two groups: group A (≤5 mL; n = 146) and group B (>5 mL; n = 170). The visual analogue scale (VAS) for pain and the Roland-Morris Disability Questionnaire (RDQ) scores were compared between the two groups at 1 week and at 1, 6, 12, and 24 months after PVP. The incidence of cement leakage into the intervertebral discs was evaluated by a postoperative lateral radiograph assessment. Patients were evaluated for new fractures 1 and 2 years after PVP or when new fractures were suspected. Among the 316 patients enrolled, 245 completed the clinical research. No difference between groups A and B in terms of the VAS, RDQ, and rate of complications at all time points after surgery was observed. The presence of intervertebral disc leakage was a relative risk (RR) for subsequent total vertebral fracture (RR, 6.42; 95% confidence interval (CI), 2.72-14.19; P < 0.0001) and adjacent vertebral fracture (RR, 8.03; 95% CI, 2.74-23.54; P = 0.0001). A high volume of bone cement may increase the rate of subsequent total and adjacent vertebral fractures. However, the occurrence of intervertebral disc leakage is the principal risk factor for these negative outcomes of PVP.

miRNAs from Plasma Extracellular Vesicles Are Signatory Noninvasive Prognostic Biomarkers against Atherosclerosis in LDLr-/-Mice.

Circular microRNAs (miRNAs) have become central in pathophysiological conditions of atherosclerosis (AS). However, the biomarkers for diagnosis and therapeutics against AS are still unclear. The atherosclerosis models in low-density lipoprotein receptor deficiency (LDLr-/-) mice were established with a high-fat diet (HFD). The extraction kit isolated extracellular vesicles from plasma. Total RNAs were extracted from LDLr-/- mice in plasma extracellular vesicles. Significantly varying miRNAs were detected by employing Illumina HiSeq 2000 deep sequencing technology. Target gene predictions of miRNAs were employed by related software that include RNAhybrid, TargetScan, miRanda, and PITA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) further analyzed the intersection points of predicted results. The results showed that the HFD group gradually formed atherosclerotic plaques in thoracic aorta compared with the control group. Out of 17, 8 upregulated and 9 downregulated miRNAs with a significant difference were found in the plasma extracellular vesicles that were further cross-examined by sequencing and bioinformatics analysis. Focal adhesion and Ras signaling pathway were found to be the most closely related pathways through GO and KEGG pathway analyses. The 8 most differentially expressed up- and downregulated miRNAs were further ascertained by TaqMan-based qRT-PCR. TaqMan-based qRT-PCR and in situ hybridization further validated the most differentially expressed miRNAs (miR-378d, miR-181b-5p, miR-146a-5p, miR-421-3p, miR-350-3p, and miR-184-3p) that were consistent with deep sequencing analysis suggesting a promising potential of utility to serve as diagnostic biomarkers against AS. The study gives a comprehensive profile of circular miRNAs in atherosclerosis and may pave the way for identifying biomarkers and novel targets for atherosclerosis.