Mathematical Analysis of FLASH Effect Models Based on Theoretical Hypotheses

Objective: Clinical applications of FLASH radiotherapy require a model to describe how the FLASH radiation features and other related factors determine the FLASH effect. Mathematical analysis of the models can connect the theoretical hypotheses with the radiobiological effect, which provides the foundation for establishing clinical application models. Moreover, experimental and clinical data can be used to explore the key factors through mathematical analysis. Approach: We abstract the complex models of the oxygen depletion hypothesis and radical recombination-antioxidants hypothesis into concise equations. Then, the equations are solved to analyze how the radiation features and other factors influence the FLASH effect. Additionally, we show how to implement the hypotheses' models in clinical application with the example of fitting the experimental data and predicting the biological effects. Main results: The formulas linking the physical, chemical and biological factors to the FLASH effect are obtained through mathematical solutions and analysis of the equations. These formulas will enable the utilization of experimental and clinical data in clinical applications by fitting the data to the formulas. Based on this analysis, we propose suggestions for systematic experiments toward clinical FLASH radiotherapy. Significance: Our work derives the mathematical formulas that elucidate the relationship between factors in the oxygen depletion hypothesis and radical recombination-antioxidants hypothesis, and the FLASH effect. These mathematical formulas provide the theoretical basis for developing the clinical application models for FLASH radiotherapy. Furthermore, the analysis of these hypotheses indicates the key factors of the FLASH effect and offers references for the design of systematic experiments toward clinical applications

Clinical study of Bian-shi therapy to mitigate insomnia symptoms in young and middle-aged patients with chronic insomnia by regulating neurotransmitters

Objective To investigate the therapeutic mechanism of Bian-shi therapy in improving sleep quality in young and middle-aged patients with chronic insomnia. Methods 40 young and middle-aged patients with chronic insomnia were randomly divided into the western medicine group （n = 20） and Bian-shi group （n = 20）. In the western medicine group， patients were orally treated with zopiclone （7.5 mg， oral administration before bedtime）， and those in the Bian-shi group were treated with placebo and Bian-shi therapy （once a week， 40 min a time， 4 times in total）. The changes of Pittsburgh Sleep Quality Index （PSQI）， and serum melatonin， acetylcholine and norepinephrine before and after 30 d treatment were analyzed and compared between two groups. Results After 30 d treatment， PSQI scores were significantly lower compared with those before treatment in two groups （both P < 0.05）. In the Bian-shi group， PSQI scores were more significantly decreased than those in the western medicine group （all P < 0.05）. After 30 d treatment， serum levels of melatonin and acetylcholine were significantly higher， whereas norepinephrine levels were significantly lower than those before treatment in two groups （all P < 0.05）. In the Bian-shi group， serum levels of melatonin and acetylcholine were significantly higher， whereas norepinephrine levels were significantly lower compared with those in the western medicine group （all P < 0.05）. Conclusions Bian-shi therapy can effectively improve the sleep quality of young and middle-aged patients with chronic insomnia， which yields higher clinical efficacy than that of zopiclone tablets. Multiple neurotransmitters may be involved in the mechanism of Bian-shi therapy to mitigate chronic insomnia symptoms

Secondary Production of Gaseous Nitrated Phenols in Polluted Urban Environments

Nitrated phenols (NPs) are important atmospheric pollutants that affect air quality, radiation, and health. The recent development of the time-of-flight chemical ionization mass spectrometer (ToF-CIMS) allows quantitative online measurements of NPs for a better understanding of their sources and environmental impacts. Herein, we deployed nitrate ions as reagent ions in the ToF-CIMS and quantified six classes of gaseous NPs in Beijing. The concentrations of NPs are in the range of 1 to 520 ng m(-3). Nitrophenol (NPh) has the greatest mean concentration. Dinitrophenol (DNP) shows the greatest haze-to-clean concentration ratio, which may be associated with aqueous production. The high concentrations and distinct diurnal profiles of NPs indicate a strong secondary formation to overweigh losses, driven by high emissions of precursors, strong oxidative capacity, and high NOx levels. The budget analysis on the basis of our measurements and box-model calculations suggest a minor role of the photolysis of NPs (Peer reviewe

Petrochemical and Industrial Sources of Volatile Organic Compounds Analyzed via Regional Wind-Driven Network in Shanghai

Due to the development of industrialization and urbanization, secondary pollution is becoming increasingly serious in the Yangtze River Delta. Volatile organic compounds (VOCs) are key precursors of the near-surface ozone, secondary organic aerosol (SOA), and other secondary pollutants. In this study, we chose a serious ozone pollution period (01 May–31 July 2017) in Jinshan, which is a petrochemical and industrial area in Shanghai. We explored the VOCs distribution characteristics and contribution to secondary pollutants via constructing a regional network based on wind patterns. We determined that dense pollutants were accumulated at adjacent sites under local circulation (LC), and pollution from petrochemical discharge was more serious than industry for all sites under southeast (SE) wind. We also found that cyclopentane, o-xylene, m/p-xylene, 1-3-butadiene, and 1-hexene were priority-controlled species as they were most vital to form secondary pollutants. This study proves that regional network analysis can be successfully applied to explore pollution characteristics and regional secondary pollutants formation

Modeling of DNA Damage Repair and Cell Response in Relation to p53 System Exposed to Ionizing Radiation

Repair of DNA damage induced by ionizing radiation plays an important role in the cell response to ionizing radiation. Radiation-induced DNA damage also activates the p53 system, which determines the fate of cells. The kinetics of repair, which is affected by the cell itself and the complexity of DNA damage, influences the cell response and fate via affecting the p53 system. To mechanistically study the influences of the cell response to different LET radiations, we introduce a new repair module and a p53 system model with NASIC, a Monte Carlo track structure code. The factors determining the kinetics of the double-strand break (DSB) repair are modeled, including the chromosome environment and complexity of DSB. The kinetics of DSB repair is modeled considering the resection-dependent and resection-independent compartments. The p53 system is modeled by simulating the interactions among genes and proteins. With this model, the cell responses to low- and high-LET irradiation are simulated, respectively. It is found that the kinetics of DSB repair greatly affects the cell fate and later biological effects. A large number of DSBs and a slow repair process lead to severe biological consequences. High-LET radiation induces more complex DSBs, which can be repaired by slow processes, subsequently resulting in a longer cycle arrest and, furthermore, apoptosis and more secreting of TGFβ. The Monte Carlo track structure simulation with a more realistic repair module and the p53 system model developed in this study can expand the functions of the NASIC code in simulating mechanical radiobiological effects

Paraphlomis yingdeensis (Lamiaceae), a new species from Guangdong (China)

Paraphlomis yingdeensis (Lamiaceae), a new species from the limestone area in northern Guangdong Province, China, is described and illustrated. Phylogenetic analyses, based on two nuclear DNA regions (ITS and ETS) and three plastid DNA regions (rpl32-trnL, rps16 and trnL-trnF), suggest that P. yingdeensis represents a distinct species in Paraphlomis. Morphologically, P. yingdeensis is similar to P. foliata subsp. montigena and P. nana, but can be distinguished from the former by its densely villous lamina and calyx, not decurrent base of lamina and bristle-like-acuminate apex of calyx teeth, and distinguished from the latter by its significantly taller plant (15–20 cm vs. 1–5 cm) and larger lamina (6.2–16.5 × 4–11.5 vs. 2–7 × 1.5–4 cm), densely villous stem, lamina and calyx and yellow corolla

Astaxanthin Alleviates Foam Cell Formation and Promotes Cholesterol Efflux in Ox-LDL-Induced RAW264.7 Cells via CircTPP2/miR-3073b-5p/ABCA1 Pathway

Atherosclerosis (AS) is a common cardiovascular disease and remains the leading cause of death in the world. It is generally believed that the deposition of foam cells in the arterial wall is the main cause of AS. Moreover, promoting cholesterol efflux and enhancing the ability of reverse cholesterol transport (RCT) can effectively inhibit the formation of foam cells, thereby preventing the occurrence and development of AS. Astaxanthin, with a powerful antioxidant ability, has a potential role in the prevention of atherosclerosis, but how it works in preventing atherosclerosis remains unknown. Here, our experimental results suggest that astaxanthin can upregulate the expression of circular RNA tripeptidyl-peptidase II (circTPP2) and eventually promote cholesterol efflux by modulating ATP-binding cassette subfamily A member 1 (ABCA1). The expression of ABCA1 was significantly suppressed after knocking down circTPP2 in macrophage-derived foam cells. In addition, the experimental results showed that circTPP2 could downregulate the expression of microRNA-3073b-5p (miR-3073b-5p), and ABCA1 was identified as the target gene of miR-3073b-5p. In conclusion, the circTPP2/miR-3073b-5p/ABCA1 axis may be the specific mechanism of astaxanthin promoting cholesterol efflux

Unexpected fast radical production emerges in cool seasons: implications for ozone pollution control

Ozone is a crucial air pollutant that damages human health and vegetation. As it is related to the photo-oxidation of the nitrogen oxides and volatile organic compounds, the summertime reduction of these precursors is the primary focus of current ozone mitigation strategies. During ozone pollution episodes in eastern China, an observed accumulation of daily total oxidants (Ox=NO2+O3) in cool seasons (spring and autumn: 60 ppb and winter 40 ppb) is comparable to that in summer (60 ppb), indicating fast photochemical production of secondary pollutants including ozone over the year. Unrecognized fast radical primary productions are found to counteract the increased termination of hydroxyl radical and unfavorable meteorological conditions to maintain the rapid total oxidant formations in cool seasons. Elucidating and regulating the primary radical sources may be critical for the secondary air pollution control in cool seasons

β-Elemene Suppresses Obesity-Induced Imbalance in the Microbiota-Gut-Brain Axis

As a kind of metabolically triggered inflammation, obesity influences the interplay between the central nervous system and the enteral environment. The present study showed that β-elemene, which is contained in various plant substances, had effects on recovering the changes in metabolites occurring in high-fat diet (HFD)-induced obese C57BL/6 male mice brains, especially in the prefrontal cortex (PFC) and hippocampus (HIP). β-elemene also partially reversed HFD-induced changes in the composition and contents of mouse gut bacteria. Furthermore, we evaluated the interaction between cerebral metabolites and intestinal microbiota via Pearson correlations. The prediction results suggested that Firmicutes were possibly controlled by neuron integrity, cerebral inflammation, and neurotransmitters, and Bacteroidetes in mouse intestines might be related to cerebral aerobic respiration and the glucose cycle. Such results also implied that Actinobacteria probably affected cerebral energy metabolism. These findings suggested that β-elemene has regulatory effects on the imbalanced microbiota-gut-brain axis caused by obesity and, therefore, would contribute to the future study in on the interplay between cerebral metabolites from different brain regions and the intestinal microbiota of mice