Phenomics (Cham, Switzerland)最新文献

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.

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.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00187-5.

The collection of big data on skin and appendage phenotypes has revolutionized the field of personalized diagnosis and treatment by enabling the evaluation of individual characteristics and early detection of abnormalities. To establish a standardized system for collecting and measuring big data on phenotypes, a systematic categorization of measurement entries has been undertaken, accompanied by recommendations on measurement entries, environmental equipment requirements, and collection processes, tailored to the needs of different usage scenarios. Specific collection sites have also been recommended based on different index characteristics. A multi-center, multi-regional collaboration has been initiated to collect big date on phenotypes of healthy and diseased skin in the Chinese population. This data will be correlated with patient disease information, exploring the factors influencing skin phenotype, analyzing the phenotypic data features that can predict prognosis, and ultimately promoting the exploration of the pathophysiology and pathogenesis of skin diseases and therapeutic approaches. Non-invasive skin measurement robots are also in development. This consensus aims to provide a reference for the study of phenomics and the standardization of phenotypic measurements of skin and appendages in China.

Despite the established associations between sleep-related traits and major diseases, comprehensive assessment on affected disease modules and their genetic determinants is lacking. Using multiple correspondence analysis and the k-means clustering algorithm, 235,826 eligible participants were clustered into distinct unfavorable sleep patterns [short sleep duration (n = 10,073), snoring (22,419), insomnia (102,771), insomnia and snoring (62,909)] and favorable sleep pattern groups (37,654). The associations of unfavorable sleep patterns with 134 diseases were estimated using Cox regression models; and comorbidity network analyses were applied for disease module identification. Genetic determinants associated with each disease module were identified by genome-wide association studies (GWAS). During an average follow-up of 10.80 years, unfavorable sleep patterns featured by 'short sleep duration', 'snoring', 'insomnia', and 'insomnia and snoring' were associated with increased risk of 0, 9, 10, and 19 diseases, respectively. Furthermore, comorbidity network analyses categorized these affected diseases into three disease modules, characterized by predominant diseases related to digestive system, circulatory and endocrine systems (snoring-related patterns only), and musculoskeletal system (insomnia-related patterns only). Using the number of affected diseases, as an index of a person's susceptibility to each disease module [i.e., susceptible score (SS)], GWAS analyses identified five, one, and three significant loci associated with the residual SS of these aforementioned disease modules, respectively, which mapped to several potential biological pathways, including those related to hormone regulation and catecholamine uptake. In conclusion, individuals with unfavorable sleep patterns, particularly snoring and insomnia, had increased risk of multiple diseases. The identification of three major disease modules with their relevant genetic determinants may facilitate strategy development for precision prevention of future health decline.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-023-00144-8.

Increasing evidence indicates that Calumenin (CALU), which is localized in the endoplasmic reticulum, is significantly associated with tumor progression. However, the effect of CALU on patients with clear cell renal cell carcinoma (ccRCC) is unknown. By integrating multi-omics data and molecular biology experiments, we found that CALU expression was significantly increased in tumors compared with normal tissues, and the pathological grade and prognosis of patients were correlated with CALU expression. Next, knockdown or ectopic expression of CALU could affect the proliferative and invasive abilities of ccRCC cells. Moreover, immune landscape characterization revealed that CALU expression was positively associated with neutrophils and macrophages, whereas it was negatively associated with natural killer T cells and CD8⁺ T cells. Single-cell sequencing showed that the localization and binding targets of CALU mainly involved monocytes/macrophages and CD4⁺ and CD8⁺ T-cells. Sensitivity analysis of common chemotherapeutic drugs showed that high expression of CALU could sensitize chemotherapeutic drugs such as 5Z-7-Oxozeaenol, AMG-706 and Cytarabine, but could lead to drug resistance to chemotherapeutic drugs such as Embelin, Salubrinal and Tipifarnib. We demonstrated a significant correlation between high CALU expression and poor patient survival. Further, we demonstrated a correlation between CALU expression, tumor microenvironment, and the sensitivity of patients to common chemo- and immuno-therapy drugs. Thus, our results indicate that CALU could be a biomarker and designing personalized treatment approaches for ccRCC patients.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00169-7.

Little is known about the links of disturbed lipid metabolism with hyperuricemia (HUA). We aimed to investigate the associations of lipidomic profiles with uric acid (UA)/HUA and their modifying factors in middle-aged and elderly Chinese. A total of 350 lipids were quantified in 2247 community-based Chinese aged 50-70 years by high-coverage targeted lipidomics. HUA was defined by plasma UA > 420 μmol/L in men or > 360 μmol/L in women. The prevalence of HUA in this population was 10.4%. After multivariable adjustment including BMI and lifestyle, 123 lipids were significantly associated with UA, predominantly glycerolipids (GLs) and glycerophospholipids (GPs). Specifically, diacylglycerol [DAG (16:0/22:5), DAG (16:0/22:6), DAG (18:1/20:5), DAG (18:1/22:6)], phosphatidylcholine [PC (16:0/20:5)), and triacylglycerol (TAG (53:0)] were the most significant lipid signatures positively associated with HUA risk, while lysophosphatidylcholine (LPC (20:2)) was inversely associated with HUA risk (p < 0.05). Network analysis also showed a positive association between TAGs/PCs/DAGs contained module and HUA risk (p < 0.01). Notably, HUA-related lipids were associated with de novo lipogenesis fatty acids, especially 16:1n-7 (Spearman correlation coefficients = 0.32-0.41, p < 0.001). Reduced rank regression showed that increased aquatic products intake was correlated to elevated HUA risk and HUA-associated lipids; while high dairy consumption was correlated with low level of HUA-associated lipids (|factor loadings| ≥ 0.2). Moreover, mediation analyses suggested that the lipid-HUA associations were partially mediated by retinol-binding protein 4 (RBP4, mediation proportion 5-14%), an adipokine linked with dyslipidemia and insulin resistance. In conclusion, disturbed specific metabolisms of GLs and GPs were associated with high prevalent HUA, partially mediated by RBP4 and/or influenced by certain dietary factors.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00157-x.

Cancer immunotherapy has made great progress in effectively attacking or eliminating cancer. However, the challenges posed by the low reactivity of some solid tumors still remain. Macrophages, as a key component of the tumor microenvironment (TME), play an important role in determining the progression of solid tumors due to their plasticity and heterogeneity. Targeting and reprogramming macrophages in TME to desired phenotypes offers an innovative and promising approach for cancer immunotherapy. Meanwhile, the rapid development of in vivo molecular imaging techniques provides us with powerful tools to study macrophages. In this review, we summarize the current progress in macrophage reprogramming from conceptual roadmaps to therapeutic approaches, including monoclonal antibody drugs, small molecule drugs, gene therapy, and chimeric antigen receptor-engineered macrophages (CAR-M). More importantly, we highlight the significance of molecular imaging in observing and understanding the process of macrophage reprogramming during cancer immunotherapy. Finally, we introduce the therapeutic applications of imaging and reprogramming macrophages in three solid tumors. In the future, the integration of molecular imaging into the development of novel macrophage reprogramming strategies holds great promise for precise clinical cancer immunotherapy.

Pyroptosis is a newly recognized type of programmed cell death mediated by the gasdermin family and caspase. It is characterized by the formation of inflammasomes and the following inflammatory responses. Recent studies have elucidated the value of pyroptosis induction in cancer treatment. The inflammatory cytokines produced during pyroptosis can trigger immune responses to suppress malignancy. Physical approaches for cancer treatment, including radiotherapy, light-based techniques (photodynamic and photothermal therapy), ultrasound-based techniques (sonodynamic therapy and focused ultrasound), and electricity-based techniques (irreversible electroporation and radiofrequency ablation), are effective in clinical application. Recent studies have reported that pyroptosis is involved in the treatment process of physical approaches. Manipulating pyroptosis using physical approaches can be utilized in combating cancer, according to recent studies. Pyroptosis-triggered immunotherapy can be combined with the original anti-tumor methods to achieve a synergistic therapy and improve the therapeutic effect. Studies have also revealed that enhancing pyroptosis may increase the sensitivity of cancer cells to some physical approaches. Herein, we present a comprehensive review of the literature focusing on the associations between pyroptosis and various physical approaches for cancer and its underlying mechanisms. We also discussed the role of pyroptosis-triggered immunotherapy in the treatment process of physical manipulation.

Many laboratories have demonstrated that the ketogenic diet (KD) can lead to weight loss and reduced fasting glucose levels, while also increasing total serum cholesterol levels. However, it's worth noting that the specific outcomes induced by KD can vary across different research settings. Certain studies have indicated that environmental factors, such as housing conditions and the acidity of drinking water, can influence physiological parameters and gut microbes in mice. Thus, our current study aimed to investigate whether differences in housing conditions and pH levels of drinking water contribute to variations in KD-induced phenotypes and gut microbes. Our findings revealed that mice housed in conventional (CV) conditions experienced more significant weight loss, lower fasting blood glucose levels, and a greater elevation of blood cholesterol levels compared to those in the specific pathogen-free (SPF) condition. Additionally, similar differences were observed when comparing mice fed with non-acidified water versus acidified water. Furthermore, we analyzed cecum content samples using 16S rRNA sequencing to assess gut microbial composition and found that the tested environmental variables also had an impact on the gut microbial composition of KD-fed mice, which was correlated with their phenotypic alterations. In summary, both housing conditions and the pH of drinking water were identified as crucial environmental factors that influenced KD-induced changes in metabolic phenotypes and gut microbes. Our study emphasizes the importance of considering these factors in animal studies related to KD and gut microbes, as well as in other types of animal research.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00161-1.