Biology subjects

Li, Q.

Publications and source records attributed to Li, Q..

At least 307 records · Page 17Linked to original sources

bioRxiv2024

Towards genuine three-dimensional diffusion imaging with physiological motion compensation

PurposeWe aim to implement a 3D DWI sequence and show its usage on patients with new ischemic lesions. Materials and MethodsThe proposed 3D DWI sequence was implemented by integrating second-order gradient moment nulling (M2) and cardiac motion synchronization (Sync). All data were acquired on a 3T MAGNETOM Prisma scanner (Siemens Healthcare, Erlangen, Germany) using a 64 channel head and neck coil. 21 healthy volunteers underwent 3D DWI scans at 0.9 mm isotropic resolution using four motion compensation methods for comparison: no compensation (M0), M2 only, Sync only and the proposed M2+Sync method. 2D phase variation maps with different motion compensation methods were also acquired for one subject to illustrate the mechanism of the proposed method. A ghost-to-signal ratio (GSR) and blurring index was defined and compared among the four methods with repeated measures ANOVA and Tukeys test. 3D DWI was compared with 2D DWI for ADC quantification. Image quality and ischemic lesion conspicuity were evaluated with 12 patients after endovascular treatment. >ResultsWhole brain 3D DWI was achieved at 0.9 mm isotropic resolution within 5 minutes using the proposed sequence. M2+Sync achieved the lowest level of GSR and blurring along the slice direction. ADC quantification showed no statistically significant difference between M2+Sync compared to 2D DWI. 3D DWI showed similar image quality, higher lesion conspicuity and counts compared to 2D DWI. ConclusionDirect 3D DWI can be achieved by the combination of second order gradient moment nulling and cardiac synchronization.

bioengineering↗

bioRxiv2024

Haplotype-resolved genomes provide insights into the origin and function of genome diversity in bivalves

Bivalves are famed for exhibiting vast genetic diversity of poorly understood origins and functional significance. Within bivalves, oysters are an ancient group showing remarkable genetic and phenotypic variability alongside extensive adaptability, serving as an ideal system to understand the origins and functional significance of genomic diversity. Here, we reveal the divergent genomic landscape of Crassostrea oysters, characterized by a history of genome size reduction associated with transposable elements (TEs). By constructing a haplotype-resolved genome for Kumamoto oyster C. sikamea, we demonstrate the widespread presence of haplotype divergent sequences (HDS); genomic regions present in just one haplotype. Combined with population resequencing, we define the role of genomic divergence driven by TEs in shaping oyster genetic diversity. Comparisons of haplotype-resolved genomes across four bivalve orders reveal that while extensive HDS is common, its origins may differ markedly. We show that HDS are a hotspot of genetic innovation, harboring rapidly evolving genes of various evolutionary ages, while also strongly influencing gene expression phenotypes. A widespread lack of allele-specific expression shared among oyster individuals indicates that haplotype polymorphism provides a key source of expression variation, promoting phenotypic plasticity and adaptation. These findings advance understanding on the origins of genomic diversity and its role in adaptive evolution.

genomics↗

bioRxiv2024

A near-complete genome assembly of the bearded dragon Pogona vitticeps provides insights into the origin of Pogona sex chromosomes

BackgroundThe agamid dragon lizard Pogona vitticeps is one of the most popular domesticated reptiles to be kept as pets worldwide. The capacity of breeding in captivity also makes it emerging as a model species for a range of scientific research, especially for the studies of sex chromosome origin and sex determination mechanisms. ResultsBy leveraging the CycloneSEQ and DNBSEQ sequencing technologies, we conducted whole genome and long-range sequencing for a captive-bred ZZ male to construct a chromosome-scale reference genome for P. vitticeps. The new reference genome is [~]1.8 Gb in length, with a contig N50 of 202.5 Mb and all contigs anchored onto 16 chromosomes. Genome annotation assisted by long-read RNA sequencing greatly expanded the P. vitticeps lncRNA catalog. With the chromosome-scale genome, we were able to characterize the whole Z sex chromosome for the first time. We found that over 80% of the Z chromosome remains as pseudo-autosomal region (PAR) where recombination is not suppressed. The sexually differentiated region (SDR) is small and occupied mostly by transposons, yet it aggregates genes involved in male development, such as AMH, AMHR2 and BMPR1A. Finally, by tracking the evolutionary origin and developmental expression of the SDR genes, we proposed a model for the origin of P. vitticeps sex chromosomes which considered the Z-linked AMH as the master sex-determining gene. ConclusionsOur study provides novel insights into the sex chromosome origin and sex determination of this model lizard. The near-complete P. vitticeps reference genome will also benefit future study of amniote evolution and may facilitate genome-assisted breeding.

genomics↗

bioRxiv2024

Immune Cell Influence on Diffuse Large B-Cell Lymphoma: A Mendelian Randomization Analysis

ObjectiveTo elucidate the causal relationship between immune cells and diffuse large B-cell lymphoma (DLBCL), we conducted a Mendelian randomization analysis. MethodsMendelian randomization (MR) leverages genetic variants as instruments to infer causal effects from observational data. Here, we performed a two-sample MR analysis to assess the causal impact of 731 immune cell types on DLBCL. We employed various MR techniques, including the weighted median estimator (WME) and inverse variance weighting (IVW), and conducted sensitivity analyses to ensure result robustness. Additionally, reverse MR analysis was performed to explore the potential causal relationship between DLBCL and immune cells. ResultsWe identified seventeen immune features with causal links to DLBCL, categorized across various cellular groups: four in B cells, two in T cell maturation stages, six in Tregs, four in the TBNK group, and one in dendritic cells (DCs). Sensitivity analyses confirmed the absence of heterogeneity, horizontal pleiotropy, and bias in our findings. Reverse causal analysis revealed a causal association between DLBCL and one of the seventeen immune cell types identified. ConclusionsOur MR analysis of seventeen immune cell types uncovers the complex interactions between the immune system and DLBCL, providing crucial insights into the tumor microenvironment and potential avenues for targeted immunotherapy.

immunology↗

bioRxiv2024

Unique Signatures of Highly Constrained Genes Across Publicly Available Genomic Databases

Publicly available genomic databases and genetic constraint scores are crucial in understanding human population variation and the identification of variants that are likely to have a deleterious impact causing human disease. We utilized the one of largest publicly available databases, gnomAD, to determine genes that are highly constrained for only LoF, only missense, and both LoF/missense variants, identified their unique signatures, and explored their causal relationship with human conditions. Those genes were evaluated for unique patterns including their chromosomal location, tissue level expression, gene ontology analysis, and gene family categorization using multiple publicly available databases. Those highly constrained genes associated with human disease, we identified unique patterns of inheritance, protein size, and enrichment in distinct molecular pathways. In addition, we identified a cohort of highly constrained genes that are currently not known to cause human disease, that we suggest will be candidates to pursue as novel disease-associated genes. In summary, these insights not only elucidate biological pathways of highly constrained genes that expand our understanding of critical cellular proteins but also advance research in rare diseases.

genetics↗

bioRxiv2024

Characterization the gene editing with miniature nucleases TnpB, IscB and enIscB in Escherichia coli strains

DNA nucleases TnpB and IscB were regarded as new antibacterial strategy to combat the drug-resistant bacteria represented by Escherichia coli due to its specificity in targeting DNA and smallest size, but the genome-editing of TnpB/IscB in E. coli remains unclear. This study characterized the genome-editing of TnpB/IscB in E. coli strains. First, the toxicity and cleavage results showed TnpB only worked in E. coli MG1655, while IscB and enIscB could perform in ATCC9637 and BL21(DE3). Next, TnpB-based genome-editing tool was established in MG1655, while IscB/enIscB achieved in ATCC9637/BL21(DE3). The copy number of TnpB/IscB/enIscB were changed to explore the impact of editing efficiency. Moreover, the editing plasmids were successfully cured. Finally, the escaping mechanism of E. coli under editing of TnpB/IscB was revealed. Overall, this study successfully applied TnpB/IscB/enIscB to genome-editing in E. coli, which will broaden genetic manipulation toolbox in E. coli and facilitate the development of new antimicrobial drugs.

microbiology↗

bioRxiv2024

BayeSMART: Bayesian Clustering of Multi-sample Spatially Resolved Transcriptomics Data

The field of spatially resolved transcriptomics (SRT) has greatly advanced our understanding of cellular microenvironments by integrating spatial information with molecular data collected from multiple tissue sections or individuals. However, methods for multi-sample spatial clustering are lacking, and existing methods primarily rely on molecular information alone. This paper introduces BayeSMART, a Bayesian statistical method designed to identify spatial domains across multiple samples. BayeSMART leverages artificial intelligence (AI)-reconstructed single-cell level information from the paired histology images of multi-sample SRT datasets while simultaneously considering the spatial context of gene expression. The AI integration enables BayeSMART to effectively interpret the spatial domains. We conducted case studies using four datasets from various tissue types and SRT platforms and compared BayeSMART with alternative multi-sample spatial clustering approaches and a number of state-of-the-art methods for single-sample SRT analysis, demonstrating that it surpasses existing methods in terms of clustering accuracy, interpretability, and computational efficiency. BayeSMART offers new insights into the spatial organization of cells in multi-sample SRT data.

bioinformatics↗

bioRxiv2024

A single-molecule nanopore sequencing platform

Nanopore sequencing, a third-generation sequencing technology, has revolutionized the gene sequencing industry with its advantages of long reads, fast speed, real-time sequencing and analysis, and potential in detecting base modifications. This technology allows researchers to sequence longer DNA fragments in a single read, providing more comprehensive genomic information compared to previous methods. Nanopore sequencing operates on electrical signals generated by a nanopore embedded in a membrane separating two electrolyte-filled chambers. When single-stranded DNA (ssDNA) passes through the nanopore, it creates variations in the current that correspond to different DNA bases. By analyzing these current fluctuations with machine learning algorithms, the DNA sequence can be determined. In this study, we introduced several improvements to nanopore sequencing, including nanopore local chemistry sequencing, novel motor and pore proteins, chip design, and basecalling algorithms. Our new nanopore sequencing platform, CycloneSEQ, demonstrated long-duration sequencing (107 hours) on a single chip with high yield (>50 Gb). In human genomic DNA sequencing, CycloneSEQ was able to produce long reads with N50 33.6 kb and modal identity 97.0%. Preliminary findings on human whole-genome de novo assembly, variant calling, metagenomics sequencing, and single-cell RNA sequencing have further highlighted CycloneSEQs potential across different areas of genomics.

genomics↗

bioRxiv2024

Exploiting functional regions in the viral RNA genome as druggable entities

RNA-targeting compounds or small interfering RNAs (siRNAs) offer a potent means for controlling viral infections. An essential prerequisite to their design depends on identifying conserved and functional viral RNA structures in cells. Techniques that probe RNA structures in situ have been developed recently including SHAPE-MaP, which has been helpful in analyzing the secondary structures of RNA. In this study, we report on the application of SHAPE-MaP to the Porcine Epidemic Diarrhoea Virus (PEDV) RNA genome to categorize different functional regions including potential quadruplex forming sequence and target sites of siRNA. Our results show that these structures can be exploited to inhibit viral proliferation and that SHAPE-MaP is an effective method to the identification of secondary structures in RNA genomes.

genomics↗

bioRxiv2024

FACT-(H3-H4) complex stimulates Pol activity to coordinate DNA synthesis with nucleosome assembly

Deficiencies in replication-coupled (RC) nucleosome assembly often lead to reduced DNA replication rate, but the precise mechanism underlying this process remains unsolved. Here, we discovered that H3-H4, but not H2A-H2B, mediates the interaction between FACT and the primase-polymerase complex DNA Pol . This interaction stimulates the DNA polymerase activity of Pol , and is indispensable for Okazaki fragment synthesis and replication fork progression. Moreover, the Pol1-N domain of Pol provides a specific binding site for FACT and H3-H4. Furthermore, CAF-1 and Rtt106-mediated replication-coupled nucleosome assembly pathways regulate this interaction. Together, we propose that the FACT-(H3-H4)-Pol interaction acts as a "Pre-Warning System" that regulates DNA replication, ensuring proper coordination between DNA synthesis and nucleosome assembly.

molecular biology↗

bioRxiv2024

Loss function of tumor suppressor FRMD8 confers resistance to tamoxifen therapy via a dual mechanism

Approximately 40% ER-positive breast cancer patients suffer from therapeutic resistance to tamoxifen. Although reduced ER level is the major cause of tamoxifen resistance, the underlying mechanisms remain elusive. Here, we report that FRMD8 raises the level of ER at both transcriptional and post-translational layers. FRMD8 deficiency in MMTV-Cre+; Frmd8fl/fl; PyMT mice accelerates mammary tumor growth and loss of luminal phenotype, and confers tamoxifen resistance. Single-cell RNA profiling reveals that Frmd8 loss decreases the proportion of hormone-sensing differentiated epithelial cells and downregulates the levels of ER. Mechanically, on one hand, loss of FRMD8 inhibits ESR1 transcription via suppressing the expression of FOXO3A, a transcription factor of ESR1. On the other hand, FRMD8 interacts both with ER and UBE3A, and disrupts the interaction of UBE3A with ER, thereby blocking UBE3A-mediated ER degradation. In breast cancer patients, FRMD8 gene promoter is found hypermethylated and low level of FRMD8 predicts poor prognosis. Therefore, FRMD8 is an important regulator of ER and may control therapeutic sensitivity to tamoxifen in ER-positive breast cancer patients. Impact StatementTumor suppressive protein FRMD8 inhibits breast cancer progression by regulating the level of ER and has the possibility to be a potential target for overcoming tamoxifen treatment resistance.

cancer biology↗

bioRxiv2024

The study on the impact of indoleacetic acid on enhancing the ability of the rumen's original microecology to degrade aflatoxin B1.

Aflatoxin B1 (AFB1) poses a serious threat to the health of cattle and is strictly monitored in their diets. Rumen microorganisms in cattle have the ability to degrade AFB1, but this capability is limited. Enhancing the degradation capacity of the original rumen microecology for AFB1 is a novel approach. From a molecular perspective,indoleacetic-3-acid (IAA) promotes the expression of cytochromes, which can improve the degradation of AFB1. Therefore, this study aims to investigate the impact of different concentrations of IAA on the degradation of AFB1 by the rumen microecology. Experiments used rumen fluid from three adult cows as donors, and the cows were all fed the same total mixed ration. Rumen fluid was collected from these three cannulated cows before morning feeding to prepare in vitro fermentation fluid. The experiments used a completely randomized design, with each treatment repeated four times. The results showed that as the fermentation time increased, the content of AFB1 gradually decreased, with a degradation rate of up to 75.73% after 24 h. AFB1 altered the rumen fermentation pattern, with a significant reduction in the content of acetic acid (P<0.05) and a significant decrease in the acetic acid to propionic acid ratio (P<0.05). It also affected the rumen microecology, causing a significant reduction in the abundance of Ruminococcus amylophilus, Prevotella ruminicola, and Fusobacterium succinogenes (P<0.05). In addition, this study found that with the increase in the amount of IAA added, the content of AFB1 in the rumen gradually decreased. IAA enhances the degradation capacity of the original rumen microecology for AFB1, and the addition of IAA alleviates the impact of AFB1 on Ruminococcus amylophilus, Prevotella ruminicola, and Fusobacterium succinogenes in the rumen (P<0.05). Moreover, the addition of IAA can promote the stability of the rumen microecology, with significantly higher acetic acid and acetic acid to propionic acid ratios in the fermentation fluid compared to the non-added group (P<0.05). In summary, the addition of IAA can improve the degradation capacity of the rumen microecology for AFB1, providing a new solution for alleviating the impact of AFB1 on animal health.

microbiology↗

bioRxiv2024

Successive pattern in winter wheat main stem structure modeling

1.With the rise of research on functional structural plant models (FSPMs), it is particularly important to realistically describe the structural traits of a plant. In 3D FSPMs, the true structural information of the canopy can make the models estimation of functional traits more accurate. Since canopy is the medium of the crop stands that sense and respond to the external environment, accurate estimation of detailed organ sizes in crop canopy is crucial, and current FSPMs still need to be improved. Here the structure of wheat (Triticum aestivum) was measured in detail at the phytomer level. Dataset was built which covers a set of [~]100 cultivars and 11 site-year under various field managements such as sowing density, inter-row, nitrogen fertilizer and sowing date. The relationships of successive phytomer sizes were quantified and the variance was analyzed for each independent experiment, only site was found as a significant impact factor. A conceptual model based on the successive pattern was proposed and validated for detailed final phytomer sizes. Then we coupled the meteorology data - the ratio of average daily gross radiation and temperature during the emergence and architecture mature with the model. The validation has taken place three times to emphasize models independent of cultivars, sites dependent and the ability of model parameters deriving from environmental factors, respectively. The results revealed the feasibility of the newly built wheat main stem structure model with the R2 higher than 0.85. Compared with ADEL-Wheat and Sirius Quality, the model achieved better performance in blade width and blade area estimation. According to the concise and easily acquired parameters of this model, it has potential for high throughput phenotyping detail wheat canopy structure. Previous work on the relationship between blade width and circumference of apex shoot in maize illustrated that the cell number was the most likely explanation for this pattern, which means the same work holds for similar crops.

developmental biology↗

bioRxiv2024

SSRI antidepressant citalopram reverses the Warburg effect to inhibit hepatocellular carcinoma by directly targeting GLUT1

Although there is growing appreciation for effective repurposing of selective serotonin reuptake inhibitors (SSRIs) for cancer therapy, particularly hepatocellular carcinoma (HCC), efforts are hampered by limited knowledge of their molecular targets and mechanism of action. Global inverse gene-expression profiling method, drug affinity responsive target stability assay, and in silico molecular docking analysis was performed to identify the targets of SSRIs. Murine subcutaneous, orthotopic models, and patient-derived xenograft were employed to explore the therapeutic effects and underlying mechanisms of SSRIs in HCC. The clinical relevance of SSRI use was verified with real world data. SSRIs exhibit significant anti-HCC effects independent of their known target serotonin reuptake transporter. The glucose transporter 1 (GLUT1) is identified as a new target of SSRIs. Citalopram binds to and antagonizes GLUT1, resulting in reduced glycolytic flux and ATP generation. Mutant GLUT1 in the binding site E380 of citalopram compromises the inhibitory effects of citalopram on the Warburg effect and tumor growth. In preclinical models, citalopram dampens the growth kinetics of GLUT1high liver tumors and displays a synergistic effect with anti-PD-1 therapy. Retrospective analysis of health records found that SSRIs use is associated with a lower risk of metastasis among HCC patients. Our study reveals an unprecedented role of SSRIs in cancer metabolism, and establishes a rationale for repurposing SSRIs as potential anticancer drugs for HCC.

cancer biology↗

bioRxiv2024

Temporal dynamics analysis reveals that concurrent working memory load eliminates the Stroop effect through disrupting stimulus-response mapping

Concurrent verbal working memory task can eliminate the color-word Stroop effect. Previous research, based on specific and limited resources, suggested that the disappearance of the conflict effect was due to the memory information preempting the resources for distractors. However, it remains unclear which particular stage of Stroop conflict processing is influenced by working memory loads. In this study, electroencephalography (EEG) recordings with event-related potential (ERP) analyses, time-frequency analyses, multivariate pattern analyses (MVPA), and representational similarity analyses (RSA) were applied to provide an in-depth investigation of the aforementioned issue. Subjects were required to complete the single task (the classical manual color-word Stroop task) and the dual task (the Sternberg working memory task combined with the Stroop task), respectively. Behaviorally, the results indicated that the Stroop effect was eliminated in the dual-task condition. The EEG results showed that the concurrent working memory task did not modulate the P1, N450, and alpha bands. However, it modulated the sustained potential (SP), late theta (740-820 ms), and beta (920-1040 ms) power, showing no difference between congruent and incongruent trials in the dual-task condition but significant difference in the single-task condition. Importantly, the RSA results revealed that the neural activation pattern of the late theta was similar to the response interaction pattern. Together, these findings implied that concurrent working memory task eliminated the Stroop effect through disrupting stimulus-response mapping.

neuroscience↗

bioRxiv2024

Conditioned immunological memory: implication for cognition of immune cells

Associative learning refers to the process by which animals or human beings build the new relationship between two stimuli or events, which has been found throughout the animal kingdom. However, no studies have reported the associative learning in cells in the body to date. In the study, we focused on immune cells, as immunological memory is considered as one of the cardinal features of the immune system. As for a classical conditioning procedure, we designed the analogues of ginsenoside Rh1 (e.g., protopanaxadiol and panaxadiol) as the conditioned stimulus (CS) and the mcKLH-Rh1 conjugate as the unconditioned stimulus (US) and determined the CS-US association by detecting the dynamics of anti-Rh1 antibody production in serum. To test the hypothesis that immune cells also have the same associative learning ability as animals or human beings, mice were divided into control and CS group. Based on above CS and US, two groups of mice were subjected to conditioned learning, conditional memory recall, and deconditioning. When we used protopanaxadiol as the CS, the antibody response to Rh1 in the mice of CS group was slower and weaker than the control mice during conditional memory recall. Interestingly, the difference between two groups in antibody response to the immunogen disappeared during deconditioning. When we used panaxadiol as the CS, the antibody response to Rh1 in the mice of two groups was similar with that in studies regarding protopanaxadiol as the CS throughout three experimental phases. These results suggested that immune cells could acquire new association between a hapten analogue and a hapten-protein conjugate after undergoing a classical conditioning. Moreover, the conditioned immunological memory enables immune cells to make a conditioned response of humoral immunosuppression to prevent US induced immune damage. Our findings open a new frontier to explore cognitive functions of cells in the body and contribute to a novel understanding of cellular bioactivities.

immunology↗

bioRxiv2024

Beyond Static Models: The Dynamic Interplay of Facial Emotions and Attentional Scope

The interplay between emotion and attention has long been intensely scrutinized, with competing theories proposing divergent mechanisms. Building on our previous work, here we present evidence that refines these perspectives, revealing a nuanced, temporally dynamic relationship between emotional stimuli and attentional focus. Using a modified Flanker task with facial emotion cues, we demonstrate that the effects of emotional stimuli on attention evolve over time, contrary to traditional fixed-effect assumptions. Our results show distinct temporal patterns: Neutral faces elicited typical flanker effects initially, but only interference persisted later. Early-stage happy faces amplified flanker facilitation but not interference, while threat faces augmented flanker interference but not facilitation. In the late stage, flanker facilitation disappeared across all emotion conditions, and interference patterns converged, mirroring the neutral face condition. These findings indicate emotions influence on attention is more complex and dynamic than previously recognized, potentially reflecting learning or habituation processes. We propose a new framework for understanding emotion-attention interactions that transcends traditional dichotomies of attention focus and approach-avoidance, offering a more nuanced perspective on this critical cognitive interface.

neuroscience↗

bioRxiv2024

Smooth muscle expression of RNA editing enzyme ADAR1 controls vascular integrity and progression of atherosclerosis

Mapping the genomic architecture of complex disease has been predicated on the understanding that genetic variants influence disease risk through modifying gene expression. However, recent discoveries have revealed that a significant burden of disease heritability in common autoinflammatory disorders and coronary artery disease (CAD) is mediated through genetic variation modifying post-transcriptional modification of RNA through adenosine-to-inosine (A-to-I) RNA editing. This common RNA modification is catalyzed by ADAR enzymes, where ADAR1 edits specific immunogenic double stranded RNA (dsRNA) to prevent activation of the double strand RNA (dsRNA) sensor MDA5 (IFIH1) and stimulation of an interferon stimulated gene (ISG) response. Multiple lines of human genetic data indicate impaired RNA editing and increased dsRNA sensing by MDA5 to be an important mechanism of CAD risk. Here, we provide a crucial link between observations in human genetics and mechanistic cell biology leading to progression of CAD. Through analysis of human atherosclerotic plaque and culture of human coronary artery vascular smooth muscle cells (SMCs) we implicate the SMC to have a distinct requirement for RNA editing, and that MDA5 activation regulates SMC phenotypic modulation. Through generation of a conditional SMC specific Adar1 deletion mouse model on a pro-atherosclerosis background with additional constitutive deletion of MDA5 (Ifih1), and with incorporation of single cell RNA sequencing cellular profiling, we further show that Adar1 controls SMC phenotypic state by regulating Mda5 activation, is required to maintain vascular integrity, and controls progression of atherosclerosis and vascular calcification. Finally, we further corroborate our findings in a large human carotid endarterectomy dataset (Athero-Express) where we show that ISG activation is strongly associated with decreased plaque stability, increased SMC phenotypic modulation, and increased plaque calcification. Through this work, we describe a fundamental mechanism of CAD, where cell type and context specific RNA editing and sensing of dsRNA mediates disease progression, bridging our understanding of human genetics and disease causality. One Sentence SummarySmooth muscle expression of RNA editing enzyme ADAR1 regulates activation of double strand RNA sensor MDA5 in novel mechanism of atherosclerosis.

genomics↗