Senna tora is a widely used medicinal plant. Its health benefits have been attributed to the large quantity of anthraquinones, but how they are made in plants remains a mystery. To identify the genes ...responsible for plant anthraquinone biosynthesis, we reveal the genome sequence of S. tora at the chromosome level with 526 Mb (96%) assembled into 13 chromosomes. Comparison among related plant species shows that a chalcone synthase-like (CHS-L) gene family has lineage-specifically and rapidly expanded in S. tora. Combining genomics, transcriptomics, metabolomics, and biochemistry, we identify a CHS-L gene contributing to the biosynthesis of anthraquinones. The S. tora reference genome will accelerate the discovery of biologically active anthraquinone biosynthesis pathways in medicinal plants.
Current treatments for wound healing engage in passive healing processes and rarely participate in stimulating skin cell behaviors for active wound healing. Electric potential difference‐derived ...electrical fields (EFs) are known to modulate skin cell behaviors. Here, a piezoelectric dermal patch is developed that can be applied on skin wound site and EF is generated to promote wound healing. The one‐directionally aligned zinc oxide nanorod‐based piezoelectric patch generates piezoelectric potential upon mechanical deformations induced by animal motion, and induces EF at the wound bed. In vitro and in vivo data demonstrate that the piezoelectric patch promotes the wound healing process through enhanced cellular metabolism, migration, and protein synthesis. This modality may lead to a clinically relevant piezoelectric dermal patch therapy for active wound healing.
A piezoelectric patch that can be applied on skin wounds and generate electric fields (EFs) to promote wound healing is developed. The zinc oxide nanorod‐based patch generates piezoelectric potential upon skin movements, and induces EF at the wound bed. In vitro and in vivo data suggest the patch promotes skin regeneration through enhanced cellular metabolism, migration, and protein synthesis.
Predicting the risk of cardiovascular disease is the key to primary prevention. Machine learning has attracted attention in analyzing increasingly large, complex healthcare data. We assessed ...discrimination and calibration of pre-existing cardiovascular risk prediction models and developed machine learning-based prediction algorithms. This study included 222,998 Korean adults aged 40-79 years, naïve to lipid-lowering therapy, had no history of cardiovascular disease. Pre-existing models showed moderate to good discrimination in predicting future cardiovascular events (C-statistics 0.70-0.80). Pooled cohort equation (PCE) specifically showed C-statistics of 0.738. Among other machine learning models such as logistic regression, treebag, random forest, and adaboost, the neural network model showed the greatest C-statistic (0.751), which was significantly higher than that for PCE. It also showed improved agreement between the predicted risk and observed outcomes (Hosmer-Lemeshow χ
= 86.1, P < 0.001) than PCE for whites did (Hosmer-Lemeshow χ
= 171.1, P < 0.001). Similar improvements were observed for Framingham risk score, systematic coronary risk evaluation, and QRISK3. This study demonstrated that machine learning-based algorithms could improve performance in cardiovascular risk prediction over contemporary cardiovascular risk models in statin-naïve healthy Korean adults without cardiovascular disease. The model can be easily adopted for risk assessment and clinical decision making.
Background
Studies have shown that long‐term exposure to air pollution such as fine particulate matter (≤2.5 μm in aerodynamic diameter PM2.5) increases the risk of all‐cause and cardiovascular ...mortality. To date, however, there are limited data on the impact of air pollution on specific cardiovascular diseases. This study aimed to evaluate cardiovascular effects of long‐term exposure to air pollution among residents of Seoul, Korea.
Methods and Results
Healthy participants with no previous history of cardiovascular disease were evaluated between 2007 and 2013. Exposure to air pollutants was estimated by linking the location of outdoor monitors to the ZIP code of each participant's residence. Crude and adjusted analyses were performed using Cox regression models to evaluate the risk for composite cardiovascular events including cardiovascular mortality, acute myocardial infarction, congestive heart failure, and stroke. A total of 136 094 participants were followed for a median of 7.0 years (900 845 person‐years). The risk of major cardiovascular events increased with higher mean concentrations of PM2.5 in a linear relationship, with a hazard ratio of 1.36 (95% confidence interval, 1.29–1.43) per 1 μg/m3 PM2.5. Other pollutants including PM2.5–10 of CO, SO2, and NO2, but not O3, were significantly associated with increased risk of cardiovascular events. The burden from air pollution was comparable to that from hypertension and diabetes mellitus.
Conclusions
This large‐scale population‐based study demonstrated that long‐term exposure to air pollution including PM2.5 increases the risk of major cardiovascular disease and mortality. Air pollution should be considered an important modifiable environmental cardiovascular risk factor.
Tg2576 transgenic mice for Alzheimer's disease (AD) exhibited significant phenotypes for neuropathological constipation, but no research has been conducted on the association of the fecal microbiota ...with dysbiosis. The correlation between fecal microbiota composition and neuropathological constipation in Tg2576 mice was investigated by examining the profile of fecal microbiota and fecal microbiota transplantation (FMT) in 9-10-month-old Tg2576 mice with the AD phenotypes and constipation. Several constipation phenotypes, including stool parameters, colon length, and histopathological structures, were observed prominently in Tg2576 mice compared to the wild-type (WT) mice. The fecal microbiota of Tg2576 mice showed decreases in Bacteroidetes and increases in the Firmicutes and Proteobacteria populations at the phylum level. The FMT study showed that stool parameters, including weight, water content, and morphology, decreased remarkably in the FMT group transplanted with a fecal suspension of Tg2576 mice (TgFMT) compared to the FMT group transplanted with a fecal suspension of WT mice (WFMT). The distribution of myenteric neurons and the interstitial cells of Cajal (ICC), as well as the enteric nervous system (ENS) function, remained lower in the TgFMT group. These results suggest that the neuropathological constipation phenotypes of Tg2576 mice may be tightly linked to the dysbiosis of the fecal microbiota.
This study investigated the laxative effects of phlorotannins (Pt) derived from
(
) on chronic constipation by evaluating alterations in stool parameters, gastrointestinal motility, histopathological ...structure, mucin secretion, gastrointestinal hormones, muscarinic cholinergic regulation, and fecal microbiota in SD rats with loperamide (Lop)-induced constipation subjected to Pt treatment. Stool-related parameters (including stool number, weight, and water contents), gastrointestinal motility, and length of intestine were significantly enhanced in the Lop+Pt-treated group as compared to the Lop+Vehicle-treated group. A similar recovery was detected in the histopathological and cytological structure of the mid-colon of Lop+Pt-treated rats, although the level of mucin secretion remained constant. Moreover, rats with Lop-induced constipation subjected to Pt treatment showed significant improvements in water channel expression, gastrointestinal hormone secretions, and expression of muscarinic acetylcholine receptors M2/M3 (mAChRs M2/M3) and their mediators of muscarinic cholinergic regulation. Furthermore, the Lop+Pt-treated group showed a significant recovery of
,
,
, and
families in fecal microbiota. Taken together, these results provide the first evidence that exposure of SD rats with Lop-induced constipation to Pt improves the constipation phenotype through the regulation of membrane water channel expression, GI hormones, the mAChR signaling pathway, and fecal microbiota.
Senna tora is an annual herb with rich source of anthraquinones that have tremendous pharmacological properties. However, there is little mention of genetic information for this species, especially ...regarding the biosynthetic pathways of anthraquinones. To understand the key genes and regulatory mechanism of anthraquinone biosynthesis pathways, we performed spatial and temporal transcriptome sequencing of S. tora using short RNA sequencing (RNA-Seq) and long-read isoform sequencing (Iso-Seq) technologies, and generated two unigene sets composed of 118,635 and 39,364, respectively. A comprehensive functional annotation and classification with multiple public databases identified array of genes involved in major secondary metabolite biosynthesis pathways and important transcription factor (TF) families (MYB, MYB-related, AP2/ERF, C2C2-YABBY, and bHLH). Differential expression analysis indicated that the expression level of genes involved in anthraquinone biosynthetic pathway regulates differently depending on the degree of tissues and seeds development. Furthermore, we identified that the amount of anthraquinone compounds were greater in late seeds than early ones. In conclusion, these results provide a rich resource for understanding the anthraquinone metabolism in S. tora.
Abstract
Aims
Physical activity has been shown to reduce mortality in a dose-response fashion. Current guidelines recommend 500–1000 metabolic equivalent task (MET)-min per week of regular physical ...activity. This study aimed to compare the impact of leisure-time physical activity on mortality in primary versus secondary cardiovascular prevention.
Methods and results
This study included a total of 131 558 and 310 240 subjects with and without cardiovascular disease (CVD), respectively, from a population-based cohort. Leisure-time physical activity was measured by self-report questionnaires. The study subjects were followed-up for a median of 5.9 years, and the main study outcome was all-cause mortality. There was an inverse relationship between the physical activity level and the mortality risk in both groups. The benefit in the secondary prevention group was shown to be greater than that in the primary prevention group: every 500 MET-min/week increase in physical activity resulted in a 14% and 7% risk reduction in mortality in the secondary and primary prevention groups, respectively (interaction P < 0.001). In addition, while individuals without CVD benefited the most between 1 and 500 MET-min/week of physical activity, the benefit in those with CVD continued above 500 − 1000 MET-min/week. The adjusted mortality risk of individuals with CVD who performed a high level of physical activity (≥1000 MET-min/week) was shown to be comparable to or lower than that of their counterparts without CVD.
Conclusion
Individuals with CVD may benefit from physical activity to a greater extent than do healthy subjects without CVD.
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