Phenomics (Cham, Switzerland)最新文献

Asparagine-linked glycosylation protein 1 homolog (ALG1) participates in the initial stage of protein N-glycosylation and N-glycosylation has been implicated in the process of hepatocellular carcinoma (HCC) progression. However, whether ALG1 plays a role in human HCC remains unknown. In this study, the expression profile of ALG1 in tumorous and corresponding adjacent non-tumor tissues was analyzed. The relationship of ALG1 expression with clinical features and prognosis of HCC patients was also evaluated using immuno-histochemical method. Here we found ALG1 decreased in HCC tissues compared with adjacent normal liver tissues, which predicted an unfavorable prognosis. Combined with RNA interference, nascent proteome and glycoproteome were determined systematically in Huh7 cell line. Bioinformatics analysis indicated that the differentially expressed proteins participating in the response of ALG1 knockdown were most significantly associated with cell-cell adhesion. Functional studies confirmed that knockdown of ALG1 reduced cell adhesion capacity, and promoted cell migration. Furthermore, down-regulation of H8N2 (on N-glycosite N651) and H5N4S2F1 (on N-glycosite N692) from N-cadherin was identified as a feature of ALG1 knockdown. Our findings revealed that ALG1 controlled the expression of glycosylated N-cadherin and played a role in HCC migration, with implications for prognosis.

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Supplementary information: The online version contains supplementary material available at 10.1007/s43657-022-00050-5.

Genetic alterations are a major cause of microphthalmos, while novel-related genes and mutations in microphthalmos have rarely been explored. To identify the underlying genetic defect responsible for microphthalmos eyes in two three-generation Chinese families, we screened 425 genes involved in common inherited non-syndromic eye diseases with next-generation sequencing-based target capture sequencing of the two probands of two three-generation Chinese families diagnosed with microphthalmos. Variants were filtered and analyzed to identify possible disease-causing variants before Sanger sequencing validation. We enrolled two families with microphthalmos (Family 1: microphthalmos with congenital ocular coloboma and Family 2: simple microphthalmos). Two novel heterozygous mutations, Peroxidasin (PXDN) c.3165C>T (p.Pro1055Pro) and PXDN c.2640C>G (p.Arg880Arg), were found in Family 1, and Crystallin Beta B2 (CRYBB2) c.481G>A (p.Gly161Arg) was found in Family 2, but none of the mutations were found in the unaffected individuals, who were phenotypically normal. Multiple orthologous sequence alignment (MSA) revealed that the CRYBB2 p.Gly161Arg mutation was a deleterious effect mutation. In conclusion, the three novel mutations found in our study extend our current understanding of the genetic basis of microphthalmos and provide early pre-symptomatic diagnosis and emphasize the significance of genetic diagnosis of microphthalmos.

Due to inefficient diagnostic methods, inflammatory bowel disease (IBD) normally progresses into severe complications including cancer. Highly efficient extraction and identification of metabolic fingerprints are of significance for disease surveillance. In this work, we synthesized a layered titania nanosheet doped with graphitized carbon (2D-GC-mTNS) through a simple one-step assembly process for assisting laser desorption ionization mass spectrometry (LDI-MS) for metabolite analysis. Based on the synergistic effect of graphitized carbon and mesoporous titania, 2D-GC-mTNS exhibits good extraction ability including high sensitivity (< 1 fmol µL^-1) and great repeatability toward metabolites. A total of 996 fingerprint spectra were collected from hundreds of native urine samples (including IBD patients and healthy controls), each of which contained 1220 m/z metabolite features. Diagnostic model was further established for precise discrimination of patients from healthy controls, with high area under the curve value of 0.972 and 0.981 toward discovery cohort and validation cohort, respectively. The 2D-GC-mTNS promotes LDI-MS to be close to clinical application, with rapid speed, minimum sample consumption and free of sample pretreatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-022-00055-0.

Exposures to copper have become a health concern. We aim to explore the broad clinical effects of blood copper concentrations. A total of 376,346 Caucasian subjects were enrolled. We performed a Mendelian randomization and phenome-wide association study (MR-PheWAS) to evaluate the causal association between copper and a wide range of outcomes in UK Biobank, and we constructed a protein-protein interaction network. We found association between blood copper concentrations and five diseases in the overall population and nine diseases in male. MR analysis implicated a causal role of blood copper in five diseases (overall population), including prostate cancer (OR = 0.87, 95% CI 0.77-0.98), malignant and unknown neoplasms of the brain and nervous system (OR = 0.58, 95% CI 0.38-0.89), and hypertension (OR = 0.94, 95% CI 0.90-0.98), essential hypertension (OR = 0.94, 95% CI 0.90-0.98) and cancer of brain and nervous system (OR = 0.63, 95% CI 0.41-0.98). For male, except for dysphagia being newly associated with blood copper (OR = 1.39, 95% CI 1.18-1.63), other MR results were consistent with the overall population. In addition, the PPI network showed possible relationship between blood copper and four outcomes, namely brain cancer, prostate cancer, hypertension, and dysphagia. Blood copper may have causal association with prostate cancer, malignant and unknown neoplasms of the brain and nervous system, hypertension, and dysphagia. Considering that copper is modifiable, exploring whether regulation of copper levels can be used to optimize health outcomes might have public health importance.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-022-00052-3.

The concept of Yang Qi in Traditional Chinese Medicine (TCM) has many similarities with mitochondria in modern medicine. Both are indispensable to human beings and closely related to life and death. This article discusses the similarities in various aspects between mitochondria and Yang Qi, including body temperature, aging, newborns, circadian rhythm, immunity, and meridian. It is well-known that Yang Qi is vital for human health. Interestingly, decreased mitochondrial function is thought to be key to the development of various diseases. Here, we further explain diseases induced by Yang Qi deficiency, such as cancer, chronic fatigue syndrome, sleep disorder, senile dementia, and metabolic diseases, from the perspective of mitochondrial function. We aim to establish similarities and connections between two important concepts, and hope our essay can stimulate further discussion and investigation on unifying important concepts in western medicine and alternative medicine, especially TCM, and provide unique holistic insights into understanding human health.

Soil salinity is among the abiotic stressors that threaten agriculture the most, and purslane (Portulaca oleracea L.) is a dicot species adapted to inland salt desert and saline habitats that hyper accumulates salt and has high phytoremediation potential. Many researchers consider purslane a suitable model species to study the mechanisms of plant tolerance to drought and salt stresses. Here, a robust salinity stress protocol was developed and used to characterize the morphophysiological responses of young purslane plants to salinity stress; then, leaf tissue underwent characterization by distinct omics platforms to gain further insights into its response to very high salinity stress. The salinity stress protocol did generate different levels of stress by gradients of electrical conductivity at field capacity and water potential in the saturation extract of the substrate, and the morphological parameters indicated three distinct stress levels. As expected from a halophyte species, these plants remained alive under very high levels of salinity stress, showing salt crystal-like structures constituted mainly by Na⁺, Cl^-, and K⁺ on and around closed stomata. A comprehensive and large-scale metabolome and transcriptome single and integrated analyses were then employed using leaf samples. The multi-omics integration (MOI) system analysis led to a data-set of 51 metabolic pathways with at least one enzyme and one metabolite differentially expressed due to salinity stress. These data sets (of genes and metabolites) are valuable for future studies aimed to deepen our knowledge on the mechanisms behind the high tolerance of this species to salinity stress. In conclusion, besides showing that this species applies salt exclusion already in young plants to support very high levels of salinity stress, the initial analysis of metabolites and transcripts data sets already give some insights into other salt tolerance mechanisms used by this species to support high levels of salinity stress.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-022-00061-2.

While disrupted lipid metabolism is a well-established risk factor for hypertension in animal models, the links between various lipidomic signatures and hypertension in human studies remain unclear. We aimed to examine associations between plasma lipidomic profiles and prevalence of hypertension among 2248 community-living Chinese aged 50-70 years. Hypertension was defined according to 2020 International Society of Hypertension global hypertension practice guidelines and 2018 Chinese guidelines. In total, 728 plasma lipidomic species were profiled using high-coverage targeted lipidomics. After multivariate adjustment, including lifestyle, body mass index, blood lipids, and sodium intake, 110 metabolites from nine lipidomic subclasses showed significant associations with hypertension, among which phosphatidylethanolamines (PEs) had the strongest association. Eleven lipidomic signals for hypertension risk were further identified from the nine subclasses, including PE(18:0/18:2) (OR per SD, 1.49; 95% confidence intervals, 1.30-1.69), phosphatidylcholine (PC) (18:0/18:2) (1.27; 1.13-1.43), phosphatidylserine (18:0/18:0) (1.24; 1.09-1.41), lysophosphatidylinositol (18:1) (1.17; 1.06-1.29), triacylglycerol (52:5) (1.38; 1.18-1.61), diacylglycerol (16:0/18:2) (1.42; 1.19-1.69), dihydroceramide (24:0) (1.25; 1.09-1.43), hydroxyl-sphingomyelins (SM[2OH])C34:1 (1.19; 1.07-1.33), lysophosphatidylcholine (20:1) (0.86; 0.78-0.95), SM(OH)C38:1 (0.87; 0.79-0.96), and PC (18:2/20:1) (0.84; 0.75-0.94). Principal component analysis also showed that a factor mainly containing specific PEs was positively associated with hypertension (1.20; 1.09-1.33). Collectively, our study revealed that disturbances in multiple circulating lipidomic subclasses and signatures, especially PEs, were significantly associated with the prevalence of hypertension in middle-aged and elderly Chinese. Future studies are warranted to confirm our findings and determine the mechanisms underlying these associations.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-022-00057-y.

Recently, an increasing number of young never-smokers are diagnosed with lung cancer. The aim of this study is to investigate the genetic predisposition of lung cancer in these patients and discover candidate pathogenic variants for lung adenocarcinoma in young never-smokers. Peripheral blood was collected from 123 never-smoking east-Asian patients diagnosed with lung adenocarcinoma before the age of 40. Whole-exome sequencing (WES) was conducted on genomic DNA extracted from peripheral blood cells. As a result, 3,481 single nucleotide variants were identified. By bioinformatical tools and the published gene list associated with genetic predisposition of cancer, pathogenic variants were detected in ten germline genes: ATR, FANCD2, FANCE, GATA2, HFE, MSH2, PDGFRA, PMS2, SDHB, and WAS. Patients with pathogenic variants were more likely to occur in females (9/10, 90.0%) and have stage IV lung adenocarcinoma (4/10, 40%). Furthermore, germline mutations in 17 genes (ASB18, B3GALT5, CLEC4F, COL6A6, CYP4B1, C6orf132, EXO1, GATA4, HCK, KCP, NPHP4, PIGX, PPIL2, PPP1R3G, RRBP1, SALL4, and TTC28), which occurred in at least two patients, displayed potentially pathogenic effects. Gene ontology analysis further showed that these genes with germline mutations were mainly located in nucleoplasm and associated with DNA repair-related biological processes. The study provides spectrum of pathogenic variants and functional explanation for genetic predisposition of lung adenocarcinoma in young never-smokers, which sheds a light on prevention and early diagnosis of lung cancer.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-022-00062-1.

HDAC6 is involved in several biological processes related to aging-associated diseases. However, it was unknown whether HDAC6 could directly regulate lifespan and healthspan. We found that HDAC6 knockdown induced transcriptome changes to attenuate the aging changes in the Drosophila head, particularly on the inflammation and innate immunity-related genes. Whole-body knockdown of HDAC6 extended lifespan in the fly, furthermore brain-specific knockdown of HDAC6 extended both lifespan and healthspan in the fly. Our results established HDAC6 as a lifespan regulator and provided a potential anti-aging target.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-022-00045-2.

The aim of this cross-sectional survey was to analyze the semen parameters of volunteers from the Human Sperm Bank of Fudan University, as well as the related factors influencing these parameters. From January 2019 to December 2020, semen parameters from a total of 5214 men were included in this survey. The Kruskal-Wallis test was used to detect differences associated with several independent variables. A total of 5214 volunteers were included. The volunteers were registered in 33 provinces, autonomous regions, municipalities (including Macau and Taiwan) and 294 prefecture-level cities. The average age of volunteers was 27.40 years. Overall, 76.50% of the volunteers had a college education or higher. Volunteers with BMI values of 18.5-23.9 kg/m² accounted for 60.70% of participants. Semen parameters were significantly different according to season, education level, duration of abstinence, age group and BMI. The basic male fertility phenotypes (semen parameters) showed new trends in the study period, and accurate long-term tracking of male semen parameters will help researchers to better understand the changes in male fertility phenotypes (semen).