（Phenomics期刊2024年第六期封面图）

01

Deficiency of Gut-Enriched Lipase H Promotes Gut Aging and Reduces Lifespan in Drosophila

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Sun, Y., Ma, H., Zhou, X. et al. Deficiency of Gut-Enriched Lipase H Promotes Gut Aging and Reduces Lifespan in Drosophila. Phenomics 4, 531–547 (2024). https://doi.org/10.1007/s43657-024-00187-5

Abstract

Liph, a gut-enriched Lipase H encoding gene, shows decreased expression during gut aging in both fruit fly and mouse. However, whether such evolutionary conserved Liph plays a protective role in gut aging remains unknown. Here we report that knocking down CG6295, the Drosophila ortholog of the mammalian Liph, led to a shortened lifespan. Loss of CG6295 in adult fly whole body caused impaired gut integrity and function, as well as reduced gut lipid storage in Drosophila. Activation of the Toll/ immune deficiency (Imd) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) immune pathways, and the release of pro-inflammatory cytokine Upd3 (IL-6) indicated immune responses in CG6295 knockdown samples. What’s more, knockdown of Drosophila CG6295 specifically in enterocytes (ECs) led to enlarged and flattened ECs, suggesting a potential regulatory mechanism of CG6295 in gut aging. In addition, down-regulation of Liph induced senescence-associated cellular and molecular phenotypes in a rat intestine cell model, suggesting the evolutionary conserved role of Liph in gut aging. Together, we discovered Liph as a novel regulator for gut aging.

Drosophila tub-Gal4ts > CG6295 RNAi-1 lines display shortened lifespan

02

MST1R Gene Variants Predispose Individuals to Tetralogy of Fallot

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Feng, Z., Huang, X., Gao, Y. et al. MST1R Gene Variants Predispose Individuals to Tetralogy of Fallot. Phenomics 4, 548–561 (2024). https://doi.org/10.1007/s43657-024-00175-9

Abstract

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart malformation. While a few susceptibility genes for TOF have been identified, research on the genetic basis of TOF is limited. The Macrophage stimulating 1 receptor (MST1R) gene encodes the macrophage-stimulating protein receptor with tyrosine phosphatase activity that is involved in immune defense. In this study, we performed whole-exome sequencing (WES) on 10 TOF families and 50 sporadic TOF patients and identified a recessive homozygous missense mutation in MST1R, c.T2009G: p.V670G, in two offspring with TOF in a single family. Targeted sequencing of the MST1R gene showed enrichment for rare variants in 417 TOF patients compared with East Asians in Genome Aggregation Database Version 2 (gnomADv2_EAS). MST1R-deficient human induced pluripotent stem cells (hiPSCs) maintained normal pluripotency but differentiated into non-functional cardiomyocytes (CMs). Taken together, our findings indicate that MST1R may play a critical role in cardiac differentiation and genetic variations in MST1R may be associated with the pathogenesis of TOF.

Homozygous mutation in MST1R identified in a TOF family

03

Characteristics of the Corneal Endothelium in Elderly Adults with High Myopia

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Zhang, Y., Zhang, S., Zhang, K. et al. Characteristics of the Corneal Endothelium in Elderly Adults with High Myopia. Phenomics 4, 562–569 (2024). https://doi.org/10.1007/s43657-024-00186-6

Abstract

This cross-sectional study aimed to investigate the corneal endothelial characteristics in elderly individuals with high myopia. We assessed corneal endothelial characteristics in 1065 eyes of 1065 elderly patients (549 highly myopic and 516 control eyes) using non-contact specular microscopy. Confirmation of suspected Fuchs endothelial corneal dystrophy (FECD) was performed with slit-lamp and confocal microscopy. Highly myopic eyes exhibited significantly greater central endothelial cell density (ECD) and coefficient of variation (CV) (p = 0.001 and p = 0.002, respectively), and lower average cell area (AVG) and percent of hexagonality (HEX) (p = 0.014 and p < 0.001, respectively) compared to control eyes. After adjusting for age and gender, axial length (AL) was positively correlated with ECD and CV (r = 0.130, p < 0.001 and r = 0.113, p < 0.001, respectively), and was negatively correlated with AVG and HEX (r = − 0.105, p = 0.001 and r = − 0.204, p < 0.001, respectively). FECD prevalence was 4.92% in highly myopic eyes and 3.29% in controls, with more advanced cases in highly myopic eyes (p = 0.036). In conclusion, longer AL was associated with increased corneal ECD, and greater endothelial pleomorphism and polymegethism in elderly patients. Highly myopic eyes appeared to have higher prevalence and severity of FECD. The study was registered on www.clinicaltrials.gov on February 26, 2017, with the registration number NCT 03062085.

Flowchart of patients included in the study

04

Integrated Transcriptome Analysis of lncRNA, miRNA, and mRNA Reveals key Regulatory Modules for Polycystic Ovary Syndrome

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Lin, R., Zheng, S., Su, H. et al. Integrated Transcriptome Analysis of lncRNA, miRNA, and mRNA Reveals key Regulatory Modules for Polycystic Ovary Syndrome. Phenomics 4, 570–583 (2024). https://doi.org/10.1007/s43657-024-00183-9

Abstract

Polycystic ovarian syndrome (PCOS) is the most common reproductive metabolic disorder in women of reproductive age. However, the underlying mechanism is unclear, because the main symptoms vary with age and the pathogenesis is complex and multifactorial. In order to explore the gene expression and regulation networks, and identify potential biomarkers for diagnosis and treatment of PCOS, we conducted whole RNA sequencing of protein-coding genes, lncRNAs, and miRNAs in peripheral blood with case-control design. RNA sequencing and weighted gene co-expression network analysis (WGCNA) were performed on four pairs of PCOS cases and control peripheral blood samples. The results showed that there were significant differences in the expression levels of 341 mRNAs, 252 lncRNAs and 47 miRNAs between PCOS patients and control groups. Bioinformatics analysis showed that these differentially expressed genes (DEGs) were mainly involved in the metabolic, immune, endocrine, and nervous systems, and also identified potential WGCNA module related with PCOS. The DEGs of PCOS as reported in other published literatures were used to verify our DEGs in this study. These results suggest that the ceRNA regulatory relationship between miR-17-5p, LINC02213 and FCGR1A, the trans-regulatory relationship between RP11-405F3.4:IL1R1 and RP11-405F3.4:IL27, and a hub lncRNA of LINC02649 in core regulatory network, which have significant potential for PCOS research. We constructed the core WGCNA module of PCOS from the whole transcriptome of human peripheral blood and characterized the key gene characteristics of PCOS. These findings provide key insights into the candidate characteristics and mechanism elucidation of PCOS.

Significantly different transcriptome of PCOS and control peripheral blood 

05

Cohort Profile: TRacing Etiology of Non-communicable Diseases (TREND): Rationale, Progress and Perspective

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Ren, HY., Lv, Y., Ma, BN. et al. Cohort Profile: TRacing Etiology of Non-communicable Diseases (TREND): Rationale, Progress and Perspective. Phenomics 4, 584–591 (2024). https://doi.org/10.1007/s43657-024-00196-4

Abstract

The TRacing Etiology of Non-communicable Diseases (TREND) cohort is a prospective longitudinal cohort and biobank that is mainly based in Ma’anshan, Anhui Province, China. The primary aim of the study is to decipher comprehensive molecular characterization and deep phenotyping for a broad spectrum of chronic non-communicable diseases (NCDs), which focuses on providing mechanistic insights with diagnostic, prognostic and therapeutic implications. The recruitment was initiated in 2023 and is expected to complete in 2025 with 20,000 participants originated from urban and rural area. In the first phase, 3360 participants were recruited. Follow-up visits are scheduled annually and intervally for a total of 30 years. The cohort includes individuals aged over 18 years. Two participants with first-degree linkage were recruited from a household. The age distribution of recruited participants was stratified into four categories: 18–45, 45–55, 55–65, and ≥65 years, aligning with the population proportions of Ma’anshan. Meanwhile, the gender distribution was controlled by pairing men and women from the same household. Data collected at baseline includes socio-economic information, medical history, lifestyle and nutritional habits, anthropometrics, blood oxygen, electrocardiogram (ECG), heart sound, as well as blood, urine and feces tests results. Molecular profiling includes genome, proteome, metabolome, microbiome and extracellular vesicles -omics. Blood, urine and fecal samples are collected and stored at −80 °C in a storage facility for future research.

Study design and work scheme of the TREND cohort

06

 Brain Imaging and Phenotyping for the China Phenobank Project

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Bai, W. Brain Imaging and Phenotyping for the China Phenobank Project. Phenomics 4, 592–593 (2024). https://doi.org/10.1007/s43657-024-00197-3

Conclusion

Here the work in (Wang et al. 2023) offers an exciting first glimpse of the incoming large-scale phenobank for the Chinese population and describes the richness of its IDPs for conducting health-related research that can benefit the entire research community.

07

A Protocol for Body MRI/CT and Extraction of Imaging-Derived Phenotypes (IDPs) from the China Phenobank Project

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Wang, C., Wang, S., Hua, S. et al. A Protocol for Body MRI/CT and Extraction of Imaging-Derived Phenotypes (IDPs) from the China Phenobank Project. Phenomics 4, 594–616 (2024). https://doi.org/10.1007/s43657-023-00141-x

Abstract

Currently, standard protocols for body imaging and corresponding image processing pipelines in population-based cohort studies are unavailable, limiting the applications of body imaging. Based on the China Phenobank Project (CHPP), the present study described a body imaging protocol for multiple organs, including cardiac structures, liver, spleen, pancreas, kidneys, lung, prostate, and uterus, and the corresponding image processing pipelines promoted its development. Briefly, the body imaging protocol comprised a 40-min cardiac magnetic resonance imaging (MRI) scan, a 5-min computed tomography (CT) scan, a 20-min abdominal MRI scan, and a 10-min pelvic MRI scan. The recommended image processing pipeline utilized deep learning segmentation models to facilitate the analysis of large amount of data. This study aimed to provide a reference for planning studies based on the CHPP platform.

Representative images

08

Risk Analysis of Atrial Fibrillation Based on ECG Phenotypes: The RAF-ECP Study Protocol

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Wang, A., He, J., Feng, X. et al. Risk Analysis of Atrial Fibrillation Based on ECG Phenotypes: The RAF-ECP Study Protocol. Phenomics 4, 617–632 (2024). https://doi.org/10.1007/s43657-023-00151-9

Abstract

Atrial fibrillation (AF) is the most common supraventricular arrhythmia in clinical practice, and many patients exhibit silent AF. Variables based on Electrocardiogram (ECG) have shown promise in assessing AF risk in the previous study. This study protocol proposes a systematic approach, named RAF-ECP, to evaluate the role of ECG phenotypes in assessing the risk of AF. The protocol aims to standardize the definition and calculation of ECG phenotypes, ensuring consistency and comparability across different research studies and healthcare settings. Data will be collected from multiple clinical laboratories, with an anticipated sample size of 10,000 cases (lead I and II, 10 s) evenly distributed between subjects with and without AF events in one-year time frame. By analyzing ECG data and baseline information, statistical tests and machine learning classifiers will be employed to identify significant risk factors and develop a comprehensive risk assessment model for AF. The anticipated outcomes include hazard ratio values, confidence intervals, p values, as well as accuracy, sensitivity, and specificity measures. The study also discusses the clinical relevance and potential benefits of standardizing ECG phenotypes, emphasizing the need for collaboration between multiple centers to obtain diverse and representative datasets. The proposed RAF-ECP study protocol offers a novel and significant approach to understanding the impact of ECG phenotypes on AF risk assessment. Its integration of statistical analysis and machine learning techniques has the potential to advance AF research and contribute to the development of improved risk prediction models and clinical decision support tools.

The flowchart of the procedure of RAF-ECP study protocol

09

Newly Identified Genes Linked to Tetralogy of Fallot

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Wang, J., Lu, Y., Zhang, R. et al. Modulating and Imaging Macrophage Reprogramming for Cancer Immunotherapy. Phenomics 4, 401–414 (2024). https://doi.org/10.1007/s43657-023-00154-6

Conclusion

This article provides an important first link between MST1R and nonsyndromic TOF patients. This work demonstrated the potential role of MST1R in cardiac development at both the cellular and molecular levels, offering potential new insights into the genetic etiology of TOF.

END

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   排版 | 宋远丽

                   撰文 | Phenomics编辑部

   编辑 | 宋远丽

                   校审 | Phenomics编辑部

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