Phenomics (Cham, Switzerland)最新文献

For shade-intolerant plants, a reduction in the red/far-red (R:FR) light ratio signals the close proximity of competitors and triggers shade-avoidance syndrome (SAS). Auxin, brassinosteroid, gibberellin and some transcriptional regulators have been reported to regulate shade-induced hypocotyl elongation. However, little is understood regarding the coordination of these multiple regulatory pathways. Here, combining time-lapse growth rates and transcriptomic data, we demonstrate that auxin and brassinosteroid affect two phases of shade-induced rapid growth, whereas gibberellin mainly contributes to the second rapid growth phase. PHYTOCHROME-INTERACTING FACTOR 7 (PIF7) acts earlier than other PIFs. PIF4 and PIF5 modulate the second rapid growth phase. LONG HYPOCOTYL IN FAR-RED 1 (HFR1) and PIF3-LIKE 1 (PIL1) modulate two rapid growth phases. Our results reveal that hormonal and transcriptional regulatory programs act together to coordinate dynamic hypocotyl changes in an immediate response to a shade signal and provide a novel understanding of growth kinetics in a changing environment.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-022-00044-3.

Light is an important external factor that affects human circadian rhythms. This study aimed to explore the effects of different dimensions of diurnal light exposure on the physiological circadian phase shift (CPS) of the human body. A strict light exposure experiment with different timing schemes (8:00-12:00, 13:00-17:00, 18:00-22:00), durations (4 h, 8 h) and effective circadian stimulus levels (circadian stimulus: 0.35, 0.55) was performed in an enclosed laboratory. Fourteen participants, including seven males and seven females, with a mean age of 24.29 ± 2.43 (mean ± standard deviation), participated in this experiment and experienced all six lighting schemes. The results showed that both time factor (F _3,40 = 29.079, p < 0.001, the power of the sample size = 0.98) and circadian stimulus levels (T ₂₀ =  - 2.415, p = 0.025, the power of sample size = 0.76) significantly affect the CPS. On this basis, a diurnal circadian lighting accumulation (DCLA)-CPS model was proposed in the form of the Boltzmann function, and was validated by experimental data with high correlation (R ² = 0.9320, RSS = 0.1184), which provides strong support for rationally arranging the light level at different times of the day.

Hemodynamically significant patent ductus arteriosus (hsPDA) is a severe condition in newborns. Ibuprofen is an effective treatment to reduce the severe complications and the need for surgical treatment. Several single-nucleotide polymorphisms (SNPs) were related to the ibuprofen metabolism, treatment effects, and the onset of side effects. The effects of SNPs on hsPDA response after ibuprofen treatment are unknown. Therefore, in this study, we recruited hsPDA patients with standard ibuprofen treatment. Those patients had participated in China Neonatal Genomes Project (CNGP, ClinicalTrials.gov Identifier: NCT03931707) with next-generation sequencing data. We reanalyzed the sequencing data and compared the allele frequencies of known ibuprofen-related SNPs between ibuprofen Responder and Non-responder groups. In total, 185 hsPDA patients were recruited with gestational age (GA) ranging from 24 to 40 weeks. No significant differences were detected in the basic information, period of ibuprofen treatment, rate of conservative treatment, complications, and side effects between ibuprofen Responder group and Non-responder group. Totally, 17 hsPDA carried CYP2C9*3 and one with CYP2C9*2 were detected. In the GA group of more than 30 GA weeks (GA > 30 wks group), we found higher allele frequency of CYP2C9*3 in Responder group than in Non-responder group (16% vs. 0, p = 0.0391). In the GA group of less than 30 GA weeks (GA ≤ 30 wks group), the sum allele frequency of CYP2C9*3 and CYP2C9*2 had no stastical difference between two groups (Responder group vs. Non-responder group, 13% vs. 11%, p = 0.768). Therefore, we came to conclude that genetic tests of CYP2C9*3 site may benefit the prediction of ibuprofen treatment outcome for hsPDA patients with gestational age of more than 30 weeks.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-021-00028-9.

Alzheimer's disease (AD) is the leading cause of dementia in the aging population, but despite extensive research, there is no consensus on the biological cause of AD. While AD research is dominated by protein/peptide-centric research based on the amyloid hypothesis, a theory that designates dysfunction in beta-amyloid production, accumulation, or disposal as the primary cause of AD, many studies focus on metabolomics as a means of understanding the biological processes behind AD progression. In this review, we discuss mass spectrometry (MS)-based AD metabolomics studies, including sample type and preparation, mass spectrometry specifications, and data analysis, as well as biological insights gleaned from these studies, with the hope of informing future AD metabolomic studies.

Birth weight (BW) is a key determinant of infant mortality. Previous studies have reported seasonal fluctuation of BW. However, the responsible environmental factors remain disputable. High-altitude environment provides a great opportunity to test the current hypotheses due to its distinctive climate conditions. We collected BW data of  ~ 9000 Tibetan singletons born at Lhasa (elevation: 3660 m) from 2014 to 2018. Using regression models, we analyzed BW seasonality of highland Tibetans. Multivariate models with meteorological factors as independent variables were employed to examine responsible environmental factors accounting for seasonal variation. We compared BW, low-BW prevalence and sex ratio between highland and lowland populations, and we observed a significant seasonal pattern of BW in Tibetans, with a peak in winter and a trough in summer. Notably, there is a marked sex-biased pattern of BW seasonality (more striking in males than in females). Sunlight exposure in the 3rd trimester and barometric pressure exposure in the 2nd trimester are significantly correlated with BW, and the latter can be explained by seasonal change of oxygen partial pressure. In particular, due to the male-biased BW seasonality, we found a more serious BW reduction and higher prevalence of low-BW in males, and a skewed sex ratio in highlanders. The infant BW of highland Tibetans has a clear pattern of seasonality. The winter BW is larger than the summer BW, due to the longer sunlight exposure during the late-trimester. Male infants are more sensitive to hypoxia than female infants during the 2nd trimester, leading to more BW reduction and higher mortality.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-021-00038-7.

Modern Western biomedical research and clinical practice are primarily focused on disease. This disease-centric approach has yielded an impressive amount of knowledge around what goes wrong in illness. However, in comparison, researchers and physicians know little about health. What is health? How do we quantify it? And how do we improve it? We currently do not have good answers to these questions. Our lack of fundamental knowledge about health is partly driven by three main factors: (i) a lack of understanding of the dynamic processes that cause variations in health/disease states over time, (ii) an excessive focus on genes, and (iii) a pervasive psychological bias towards additive solutions. Here I briefly discuss potential reasons why scientists and funders have generally adopted a gene- and disease-centric framework, how medicine has ended up practicing "diseasecare" rather than healthcare, and present cursory evidence that points towards an alternative energetic view of health. Understanding the basis of human health with a similar degree of precision that has been deployed towards mapping disease processes could bring us to a point where we can actively support and promote human health across the lifespan, before disease shows up on a scan or in bloodwork.

MicroRNAs (miRNAs), as the small, non-coding, evolutionary conserved, and post-transcriptional gene regulators of the genome, have been highly associated with various diseases such as cancers, viral infections, and cardiovascular diseases. Several techniques have been established to detect miRNAs, including northern blotting, real-time polymerase chain reaction (RT-PCR), and fluorescent microarray platform. However, it remains a significant challenge to develop sensitive, accurate, rapid, and cost-effective methods to detect miRNAs due to their short size, high similarity, and low abundance. The electrochemical biosensors exhibit tremendous potential in miRNA detection because they satisfy feature integration, portability, mass production, short response time, and minimal sample consumption. This article reviewed the working principles and signal amplification strategies of electrochemical DNA biosensors summarized the recent improvements. With the development of DNA nanotechnology, nanomaterials and biotechnology, electrochemical DNA biosensors of high sensitivity and specificity for microRNA detection will shortly be commercially accessible.

The DEAD-box RNA helicase (DDX) family plays a critical role in the growth and development of multiple organisms. DDX1 is involved in mRNA/rRNA processing and mature, virus replication and transcription, hormone metabolism, tumorigenesis, and tumor development. However, how DDX1 functions in various cancers remains unclear. Here, we explored the potential oncogenic roles of DDX1 across 33 tumors with The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. DDX1 is highly expressed in breast cancer (BRCA), cholangiocarcinoma (CHOL), and colon adenocarcinoma (COAD), but it is lowly expressed in renal cancers, including kidney renal clear cell carcinoma (KIRC), kidney chromophobe (KICH), and kidney renal papillary cell carcinoma (KIRP). Low expression of DDX1 in KIRC is correlated with a good prognosis of overall survival (OS) and disease-free survival (DFS). Highly expressed DDX1 is linked to a poor prognosis of OS for adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), KICH, and liver hepatocellular carcinoma (LIHC). Also, the residue Ser481 of DDX1 had an enhanced phosphorylation level in BRCA and ovarian cancer (OV) but decreased in KIRC. Immune infiltration analysis exhibited that DDX1 expression affected CD8⁺ T cells, and it was significantly associated with MSI (microsatellite instability), TMB (tumor mutational burden), and ICT (immune checkpoint blockade therapy) in tumors. In addition, the depletion of DDX1 dramatically affected the cell viability of human tumor-derived cell lines. DDX1 could affect the DNA repair pathway and the RNA transport/DNA replication processes during tumorigenesis by analyzing the CancerSEA database. Thus, our pan-cancer analysis revealed that DDX1 had complicated impacts on different cancers and might act as a prognostic marker for cancers such as renal cancer.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-021-00034-x.

Serum liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], λ-glutamyl transferase [GGT] and alkaline phosphatase [ALP]) are the leading biomarkers to measure liver injury, and they have been reported to be associated with several intrahepatic and extrahepatic diseases in observational studies. We conducted a phenome-wide association study (PheWAS) to identify disease phenotypes associated with genetically predicted liver enzymes based on the UK Biobank cohort. Univariable and multivariable Mendelian randomization (MR) analyses were performed to obtain the causal estimates of associations that detected in PheWAS. Our PheWAS identified 40 out of 1,376 pairs (16, 17, three and four pairs for ALT, AST, GGT and ALP, respectively) of genotype-phenotype associations reaching statistical significance at the 5% false discovery rate threshold. A total of 34 links were further validated in Mendelian randomization analyses. Most of the disease phenotypes that associated with genetically determined ALT level were liver-related, including primary liver cancer and alcoholic liver damage. The disease outcomes associated with genetically determined AST involved a wide range of phenotypic categories including endocrine/metabolic diseases, digestive diseases, and neurological disorder. Genetically predicted GGT level was associated with the risk of other chronic non-alcoholic liver disease, abnormal results of function study of liver, and cholelithiasis. Genetically determined ALP level was associated with pulmonary heart disease, phlebitis and thrombophlebitis of lower extremities, and hypercholesterolemia. Our findings reveal novel links between liver enzymes and disease phenotypes providing insights into the full understanding of the biological roles of liver enzymes.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-021-00033-y.

Phenomics explores the complex interactions among genes, epigenetics, symbiotic microorganisms, diet, and environmental exposure based on the physical, chemical, and biological characteristics of individuals and groups. Increasingly efficient and comprehensive phenotyping techniques have been integrated into modern phenomics-related research. Multicolor flow cytometry technology provides more measurement parameters than conventional flow cytometry. Based on detailed descriptions of cell phenotypes, rare cell populations and cell subsets can be distinguished, new cell phenotypes can be discovered, and cell apoptosis characteristics can be detected, which will expand the potential of cell phenomics research. Based on the enhancements in multicolor flow cytometry hardware, software, reagents, and method design, the present review summarizes the recent advances and applications of multicolor flow cytometry in cell phenomics, illuminating the potential of applying phenomics in future studies.