Decoding microbial genomes to understand their functional roles in human complex diseases

Complex diseases such as cardiovascular disease (CVD), obesity, inflammatory bowel disease (IBD), kidney disease, type 2 diabetes (T2D), and cancer have become a major burden to public health and affect more than 20% of the population worldwide. The etiology of complex diseases is not yet clear, but they are traditionally thought to be caused by genetics and environmental factors (e.g., dietary habits), and by their interactions. Besides this, increasing pieces of evidence now highlight that the intestinal microbiota may contribute substantially to the health and disease of the human host via their metabolic molecules. Therefore, decoding the microbial genomes has been an important strategy to shed light on their functional potential. In this review, we summarize the roles of the gut microbiome in complex diseases from its functional perspective. We further introduce artificial tools in decoding microbial genomes to profile their functionalities. Finally, state-of-the-art techniques have been highlighted which may contribute to a mechanistic understanding of the gut microbiome in human complex diseases and promote the development of the gut microbiome-based personalized medicine.</p

Remnant cholesterol is associated with cardiovascular mortality

Background: Genetic, observational, and clinical intervention studies indicate that circulating levels of remnant cholesterol (RC) are associated with cardiovascular diseases. However, the predictive value of RC for cardiovascular mortality in the general population remains unclear. Methods: Our study population comprised 19,650 adults in the United States from the National Health and Nutrition Examination Survey (NHANES) (1999–2014). RC was calculated from non-high-density lipoprotein cholesterol (non-HDL-C) minus low-density lipoprotein cholesterol (LDL-C) determined by the Sampson formula. Multivariate Cox regression, restricted cubic spline analysis, and subgroup analysis were applied to explore the relationship of RC with cardiovascular mortality. Results: The mean age of the study cohort was 46.4 ± 19.2 years, and 48.7% of participants were male. During a median follow-up of 93 months, 382 (1.9%) cardiovascular deaths occurred. In a fully adjusted Cox regression model, log RC was significantly associated with cardiovascular mortality [hazard ratio (HR) 2.82; 95% confidence interval (CI) 1.17–6.81]. The restricted cubic spline curve indicated that log RC had a linear association with cardiovascular mortality (p for non-linearity = 0.899). People with higher LDL-C (≥130 mg/dL), higher RC [≥25.7/23.7 mg/dL in males/females corresponding to the LDL-C clinical cutoff point (130 mg/dL)] and abnormal HDL-C (<40/50 mg/dL in males/females) levels had a higher risk of cardiovascular mortality (HR 2.18; 95% CI 1.13–4.21 in males and HR 2.19; 95% CI 1.24–3.88 in females) than the reference group (lower LDL-C, lower RC and normal HDL-C levels). Conclusions: Elevated RC levels were associated with cardiovascular mortality independent of traditional risk factors

Nomogram to Predict Poor Outcome after Mechanical Thrombectomy at Older Age and Histological Analysis of Thrombus Composition

An easy scoring system to predict the risk of poor outcome after mechanical thrombectomy among the elderly is currently not available. Therefore, we aimed to develop a nomogram for predicting the probability of negative prognosis in aged patients with acute ischemic stroke undergoing thrombectomy. In addition, we sought to investigate the association between histological thrombus composition and stroke characteristics. To this end, we prospectively studied a developed cohort using data collected from a stroke center from November 2015 to December 2019. The main outcome was functional independence, defined as a modified Rankin Scale score≤2 at 90 days following a mechanical thrombectomy. A nomogram model based on multivariate logistic models was generated. The retrieved thrombi were stained with hematoxylin and eosin and assessed according to histological composition. Our results demonstrated that age≥72 years was independently associated with poor outcome. A total of 304 participants completed the follow-up data to generate the nomogram model. After multivariate logistic regression, five variables remained independent predictors of outcome, including older age, hemorrhagic transformation, thrombolysis in cerebral infarction score, National Institute of Health Stroke score, and neutrophil-to-lymphocyte ratio, and were used to generate the nomogram. The area under the receiver-operating characteristic curve of the model was 0.803. The clots from elderly subjects with large-artery atherosclerosis, anterior circulation, and successful recanalization groups had a higher percentage of fibrin compared to those of younger patients. This is the first nomogram to be developed and validated in a stroke center cohort for individualized prediction of poor outcome in elderly patients after mechanical thrombectomy. Clot composition provides valuable information on the underlying pathogenesis of oxidation in older patients

Cell Membrane-Coated Electrospun Fibers Enhance Keratinocyte Growth through Cell-Type Specific Interactions

Although cell membrane-coated fiber scaffolds can be useful for regenerative medicine by presenting both cell surface antigens and topographical cues, it remains unknown whether changes in cellular behavior on cell membrane-coated scaffolds are due to specific cell-cell interactions. In this work, the effects of scaffold fiber diameters and surface charges on the cell membrane coating efficiency were explored. Furthermore, fibroblast membrane-coated scaffolds improved the growth of human keratinocytes as compared to red blood cell membrane-coated and plain scaffolds. These results suggest the biofunctionality of cell membrane-coated scaffolds and the specific cell-cell interactions that are preserved to modulate cellular response.Ministry of Education (MOE)Submitted/Accepted versionThis research is supported by the Singapore MOE AcRF Tier 1 Grant (Project No. RG38/19) awarded to S.Y.C

Chromosome-Scale Genome Assembly of Fusarium oxysporum Strain Fo47, a Fungal Endophyte and Biocontrol Agent

National audienceHere, we report a chromosome-level genome assembly of Fusarium oxysporum strain Fo47 (12 pseudomolecules; contig N50: 4.52Mb), generated using a combination of PacBio long-read, Illumina pair-ended and Hi-C sequencing data. Although F. oxysporum causes vascular wilt to over 100 plant species, the strain Fo47 is classified as an endophyte and widely used as a biocontrol agent for plant disease control. The Fo47 genome carries a single accessory chromosome of 4.23 Mb, compared to the reference genome of F. oxysporum f.sp. lycopersici strain Fol4287. The high-quality assembly and annotation of the Fo47 genome will be a valuable resource for studying the mechanisms underlying the endophytic interactions between F. oxysporum and plants, as well as deciphering the genome evolution of the F. oxysporum species complex

High-quality Arabidopsis thaliana Genome Assembly with Nanopore and HiFi Long Reads

Arabidopsis thaliana is an important and long-established model species for plant molecular biology, genetics, epigenetics, and genomics. However, the latest version of reference genome still contains a significant number of missing segments. Here, we reported a high-quality and almost complete Col-0 genome assembly with two gaps (named Col-XJTU) by combining the Oxford Nanopore Technologies ultra-long reads, Pacific Biosciences high-fidelity long reads, and Hi-C data. The total genome assembly size is 133,725,193 bp, introducing 14.6 Mb of novel sequences compared to the TAIR10.1 reference genome. All five chromosomes of the Col-XJTU assembly are highly accurate with consensus quality (QV) scores > 60 (ranging from 62 to 68), which are higher than those of the TAIR10.1 reference (ranging from 45 to 52). We completely resolved chromosome (Chr) 3 and Chr5 in a telomere-to-telomere manner. Chr4 was completely resolved except the nucleolar organizing regions, which comprise long repetitive DNA fragments. The Chr1 centromere (CEN1), reportedly around 9 Mb in length, is particularly challenging to assemble due to the presence of tens of thousands of CEN180 satellite repeats. Using the cutting-edge sequencing data and novel computational approaches, we assembled a 3.8-Mb-long CEN1 and a 3.5-Mb-long CEN2. We also investigated the structure and epigenetics of centromeres. Four clusters of CEN180 monomers were detected, and the centromere-specific histone H3-like protein (CENH3) exhibited a strong preference for CEN180 Cluster 3. Moreover, we observed hypomethylation patterns in CENH3-enriched regions. We believe that this high-quality genome assembly, Col-XJTU, would serve as a valuable reference to better understand the global pattern of centromeric polymorphisms, as well as the genetic and epigenetic features in plants