ABSTRACT
According to the theory of five movements and six climates, the innate constitution plays a crucial role in determining the underlyingpa thological mechanisms of diseases later in life. Previous studies have demonstrated a close association between the constitution, as defined by the theory of five movements and six climates, and the development of various types of tumors. Furt hermore,the tumorsubtype determined by the constitution has prognostic implications. This highlights the potential of utilizing the fivemovements and six climates theory to guide the implementation of precision medicine strategies in thefield of oncology. However, no resear ch has yet been conducted to investigate the use of this theory in guiding the development of tumor molecular classification and precisi onmedicine strategies. The objective of this research is to uncover the biological characteristics of each constitution within a pancanc ercohort and identify potential anti-tumor drugs that are applicable to patients with different constitutional types. By doing so, we aimto c ontribute to the establishment of a precision medicine strategy for tumors derived from the original concepts of traditional Chi nesemedicine(TCM). In this study, we obtainedpan-cancer Bulk RNA-Seq data from UCSC Xena, GWAS cohort data from the UKBiobank, and cis-eQTLs data from eQ TLGen and GTEx V8. We employed machine learning methods to screen for hub genes associated with each constitution. Subsequently, we utilized informatics tools to explore the biological characteristics of each constitut iondefined by the theory of five movements and six bioclimates. Further, potential anti-tumor drugs suitable for patients with differen tconstitutional types were identified through mendelian randomization, molecular docking, and drug-like prediction techniques. Withinthe pan-cancer cohort, significant differences were observed among different constitutions in terms of progression-free interval, biological f unctions, immune cell abundance, tumor drug sensitivity, and immunotherapy response. These findings suggest that the five movements and six climates theory can guide tumor molecular classification and the development of precision medicine strategies. Moreover,the biological characteristics inherent to each constitution partially shed light on the scientific implications of Chinese medicinetheories, offering a fresh perspective towards clinical cancer treatment. Through molecular docking and drug-like prediction, several po tential anti-tumor drugs such as 17-beta-estradiol, serotonin, trans-resveratrol, and linoleic acid were identified. Overall, the util izationof multi-omics approaches pro vides a powerful tool to unravel the scientific foundations of TCM theories. The elucidation of themu lti-omics features associated witheach constitution in tumors serves as the basis for applying the five movements and six climates theoryto tumor molecular classification and the development of precision medicine strategies.
Subject(s)
Neoplasms , Humans , Neoplasms/genetics , Neoplasms/drug therapy , Precision Medicine , RNA-Seq , Medicine, Chinese Traditional , Body Constitution/geneticsABSTRACT
Air pollution exerts crucial influence on crop yields and impacts regional and global food supplies. Here we employ a statistical model using satellite-based observations and flexible functional forms to analyse the synergistic effects of reductions in ozone and aerosols on China's food security. The model consistently shows that ozone is detrimental to crops, whereas aerosol has variable effects. China's maize, rice and wheat yields are projected to increase by 7.84%, 4.10% and 3.43%, respectively, upon reaching two air quality targets (60 µg m-3 for peak-season ozone and 35 µg m-3 for annual fine particulate matter). Average calories produced from these crops would surge by 4.51%, potentially allowing China to attain grain self-sufficiency 2 years earlier than previously estimated. These results show that ozone pollution control should be a high priority to increase staple crop edible calories, and future stringent air pollution regulations would enhance China's food security.
Subject(s)
Air Pollution , Ozone , Quality Improvement , Air Pollution/prevention & control , Ozone/analysis , Crops, Agricultural , China , Food SecurityABSTRACT
BACKGROUND: Recently, there has been a great deal interest in cuproptosis, a form of programmed cell death that is mediated by copper. The specific mechanism through which cuproptosis-related genes impact the development of colorectal cancer (CRC) remains unknown. METHODS: Here, we combined bulk RNA-seq with scRNA-seq to investigate the CRGs functions within CRC. A number of 61 cuproptosis-related genes were chosen for further investigation. Nine prognostic CRGs were identified by Lasso-Cox. The RiskScore was created and the patients have been separated into two different groups, low- and high-RiskScore group. The CIBERSORT, ESTIMATE, MCP-counter, TIDE, and IPS have been employed to score the TME, and GSVA and GSEA were utilized to evaluate the pathway within the both groups. Further, we used cell communication analysis to explore the tumor microenvironment remodeling mechanisms of the COX17 and DLAT based on scRNA-seq. Finally, we used IHC and qPCR to validate the expression of COX17 and DLAT. RESULTS: AOC3, CCS, CDKN2A, COX11, COX17, COX19, DLD, DLAT, and PDHB have been recognized as prognostic CRGs in CRC. The high-risk group exhibited the worst prognosis, an immune-deficient phenotype, and were more resistant to ICB treatment. Further, scRNA-seq analysis revealed that elevated expression of COX17 in CD4-CXCL13Tfh could contribute to the immune evasion while DLAT had the opposite effect, reversing T cell exhaustion and inducing pyroptosis to boost CD8-GZMKT infiltration. CONCLUSIONS: The current investigation has developed a prognostic framework utilizing cuproptosis-related genes that is highly effective in predicting prognosis, TME type, and response to immunotherapy in CRC patients. Furthermore, our study reveals a novel finding that elevated levels of COX17 expression within CD4-CXCL13 T cells in CRC mediates T cell exhaustion and Treg infiltration, while DLAT has been found to facilitate the anti-tumor immunity activation through the T cell exhaustion reversal and the induction of pyroptosis.
Subject(s)
Colorectal Neoplasms , Tumor Microenvironment , Humans , RNA-Seq , Prognosis , Tumor Microenvironment/genetics , Genes, p16 , Apoptosis , Copper , Colorectal Neoplasms/geneticsABSTRACT
The United States of America (USA) was afflicted by extreme heat in the summer of 2021 and some states experienced a record-hot or top-10 hottest summer. Meanwhile, the United States was also one of the countries impacted most by the coronavirus disease 2019 (COVID-19) pandemic. Growing numbers of studies have revealed that meteorological factors such as temperature may influence the number of confirmed COVID-19 cases and deaths. However, the associations between temperature and COVID-19 severity differ in various study areas and periods, especially in periods of high temperatures. Here we choose 119 US counties with large counts of COVID-19 deaths during the summer of 2021 to examine the relationship between COVID-19 deaths and temperature by applying a two-stage epidemiological analytical approach. We also calculate the years of life lost (YLL) owing to COVID-19 and the corresponding values attributable to high temperature exposure. The daily mean temperature is approximately positively correlated with COVID-19 deaths nationwide, with a relative risk of 1.108 (95% confidence interval: 1.046, 1.173) in the 90th percentile of the mean temperature distribution compared with the median temperature. In addition, 0.02 YLL per COVID-19 death attributable to high temperature are estimated at the national level, and distinct spatial variability from -0.10 to 0.08 years is observed in different states. Our results provide new evidence on the relationship between high temperature and COVID-19 deaths, which might help us to understand the underlying modulation of the COVID-19 pandemic by meteorological variables and to develop epidemic policy response strategies.
ABSTRACT
As a result of the pressure from population explosion, agricultural land resources require further protecting and rationally utilizing. Intercropping technique has been widely applied for agricultural production to save cultivated area, improve crop quality, and promote agriculture economy. In this study, we employed high-performance liquid chromatography (HPLC) and ultraviolet-visible spectroscopy (UV-vis) combined with chemometrics for determination and qualitative evaluation of several kinds of intercropping system with Gentiana rigescens Franch. ex Hemsl. (GR), which is used as an hepatic protector in local communities in China. Results revealed that GR in a Camellia sinensis intercropping system contained most gentiopicroside, sweroside, and total active constituents (six chemical indicators), whose content reached 91.09 ± 3.54, 1.03 ± 0.06, and 104.05 ± 6.48 mg g(-1), respectively. The two applied quantitative and qualitative methods reciprocally verified that GR with 2 years of growth period performed better in terms of quality than 1 year, collectively.
Subject(s)
Agriculture/methods , Camellia sinensis , Gentiana/chemistry , Iridoid Glucosides/analysis , Plant Extracts/chemistry , China , Chromatography, High Pressure Liquid/methods , Plants, Medicinal , TeaABSTRACT
Gentisides are a class of chemical compounds which is considered as potential therapeutic substance for treatment of neurodegenerative disorders. The heat reflux extraction conditions were optimized for seven kinds of gentisides from the root and rhizome of Gentiana rigescens Franch. ex Hemsl. by employing response surface method. Based on univariate test, a Box-Behnken design (BBD) was applied to the survey of relationships between response value (gentisides yield) and independent variables which were chosen from various extraction processes, including extraction temperature, extraction time, and solvent-material ratio. The optimized conditions for this extraction are as follows: extraction time of 3.40 h, extraction temperature of 74.33°C, and ratio of solvent to raw material of 10.21 : 1 mL/g. Verification assay revealed that the predicted value (99.24%) of extraction parameters from this model was mainly conformed to the experimentally observed values (98.61 ± 0.61).