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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2021年第2期22卷 123-135页

作者： Dan MU Huaguang QIN Mengjie JIAO Shaogui HUA tingzhe sun School of Life Sciences the Province Key Laboratory of the Biodiversity Study and Ecology Conservation in Southwest AnhuiAnqing Normal UniversityAnqing 246133China

Ischemic stroke presents a leading cause of mortality and morbidity worldwide.Theaflavic acid(TFA)is a theaflavin isolated from black tea that exerts a potentially neuro-protective effect.However,the dynamic properties of TFA-mediated protection remain largely unknown.In the current study,we evaluated the function of TFA in the mitochondria apoptotic pathway using mathematical modeling.We found that TFA-enhanced B-cell lymphoma 2(Bcl-2)overexpression can theoretically give rise to bistability.The bistability is highly robust against parametric stochasticity while also conferring considerable variability in survival threshold.Stochastic simulations faithfully match the TFA dose response pattern seen in experimental studies.In addition,we identified a dose-and time-dependent synergy between TFA and nimodipine,a clinically used neuro-protective drug.This synergistic effect was enhanced by bistability independent of temporal factors.Precise application of pulsed doses of TFA can also promote survival compared with sustained TFA treatment.These data collectively demonstrate that TFA treatment can give rise to bistability and that synergy between TFA and nimodipine may offer a promising strategy for developing therapeutic neuro-protection against ischemic stroke.

关键词： Theaflavic acid(TFA) Nimodipine Ischemic stroke Apoptosis Synergy

Cell-death-mode switch from necrosis to apoptosis in hydrogen peroxide treated macrophages

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Science China(Life Sciences) 2010年第10期53卷 1196-1203页

作者： LIN XuZhu sun tingzhe CAI MeiHong SHEN PingPing State Key Laboratory of Pharmaceutical Biotechnology Department of BiochemistrySchool of Life ScienceNanjing UniversityNanjing 210093China

Cell death is typically defined either as apoptosis or necrosis. Because the consequences of apoptosis and necrosis are quite different for an entire organism, the investigation of the cell-death-mode switch has considerable clinical significance. The existence of a necrosis-to-apoptosis switch induced by hydrogen peroxide in macrophage cell line RAW 264.7 cells was confirmed by using flow cytometry and fluorescence microscopy. With the help of computational simulations, this study predicted that negative feedbacks between NF-κB and MAPKs are implicated in converting necrosis into apoptosis in macrophages exposed to hydrogen peroxide, which has significant implications.

关键词： macrophage hydrogen peroxide apoptosis necrosis cell-death-mode switch

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以方差分析为例探讨p值决策的局限性

鲁东大学学报（自然科学版） 2022年第2期38卷 152-157页

作者：孙廷哲安庆师范大学生命科学学院安徽安庆246133

方差分析适用于比较多组数据间均值差异,是一种重要的统计方法。多数生物学文献及教材中只依赖统计显著性进行决策而忽略效应量和统计功效。本文以方差分析为例,运用MATLAB软件对方差分析的效应量和统计功效进行随机模拟,旨在为基于方... 详细信息

方差分析适用于比较多组数据间均值差异,是一种重要的统计方法。多数生物学文献及教材中只依赖统计显著性进行决策而忽略效应量和统计功效。本文以方差分析为例,运用MATLAB软件对方差分析的效应量和统计功效进行随机模拟,旨在为基于方差分析的统计推断提供参考。

关键词：方差分析 MATLAB 效应量统计功效

基于p53信号转导网络数学模型研究热疗联合放疗在肿瘤治疗中的协同效应

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中国药科大学学报 2021年第3期52卷 361-370页

作者：孙廷哲安庆师范大学生命科学学院安庆246133

基于p53信号转导网络数学模型研究温度和辐射在调控p53动力学行为过程中的协同效应。利用时滞微分方程构建p53动力学模型,使用加速τ-leap算法进行随机模拟分析,采用Loewe和Bliss协同指数计算协同性,用MATLAB软件进行数值模拟。结果显示... 详细信息

基于p53信号转导网络数学模型研究温度和辐射在调控p53动力学行为过程中的协同效应。利用时滞微分方程构建p53动力学模型,使用加速τ-leap算法进行随机模拟分析,采用Loewe和Bliss协同指数计算协同性,用MATLAB软件进行数值模拟。结果显示,在较低温下,p53脉冲的振幅和特征基音随温度发生转变。p53脉冲的振幅和周期具有较大的变异性。在39℃以下,p53首个脉冲的振幅随温度升高而增加,而p53的特征基音则随着温度升高而降低。较温和的高温环境(≥41℃)则破坏了p53脉冲,p53蛋白水平呈现持续累积。随着温度的升高,自相关图谱中的周期行为逐渐消失。以p53的累积值和最大值作为评价指标,温度和辐射剂量可产生显著的协同作用。另外,温度对p53动力学的影响是可逆的。总之,温度可显著影响p53的动力学特征。在肿瘤治疗中,热疗亦可为放疗提供有益的帮助。

关键词： p53 数学模型热疗放疗 DNA损伤肿瘤

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DNA双链断裂损伤修复的随机模型研究

中山大学学报（自然科学版） 2015年第5期54卷 109-114页

作者：孙廷哲崔隽安庆师范学院生命科学学院安徽安庆246011 基因工程教育部重点实验室∥中山大学生命科学学院广东广州510275

DNA双链断裂是一种非常严重的DNA损伤。对DNA双链断裂有效的修复对于维持基因组的稳定至关重要。对DNA双链断裂修复的动力学研究一直得到了广泛的关注。然而,以往的模型研究都没有充分考虑外源性和内源性DNA损伤修复之间的关联。因此,... 详细信息

DNA双链断裂是一种非常严重的DNA损伤。对DNA双链断裂有效的修复对于维持基因组的稳定至关重要。对DNA双链断裂修复的动力学研究一直得到了广泛的关注。然而,以往的模型研究都没有充分考虑外源性和内源性DNA损伤修复之间的关联。因此,通过在细胞周期重启后引入自发生成的随机DNA双键断裂损伤,并设定触发细胞周期阻滞的阈值,一个精细化的Monte Carlo模型被构建并可以更好的模拟受迫状态下的损伤修复过程。细胞首先修复辐射刺激造成的DNA损伤,接着在总损伤水平低于特定阈值后产生内源性的DNA损伤并可能在某特定时间段内对两种来源损伤同时进行修复。本模型综合考虑了外源性和内源性DNA损伤修复的整合效应,为其它涵盖DNA损伤修复模块的模型研究提供了基础。

关键词： DNA双链断裂 Monte Carlo模拟外源性DNA损伤内源性DNA损伤修复

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模拟新型冠状病毒肺炎无症状感染者传播风险

中山大学学报（自然科学版）（中英文） 2021年第5期60卷 103-110页

作者：孙廷哲崔隽安庆师范大学生命科学学院安徽安庆246133 中山大学生命科学学院广东广州510275

新型冠状病毒肺炎(COVID-19,coronavirus disease 2019)的大流行对人类健康造成了巨大威胁。新型冠状病毒肺炎无症状感染者在早期不易被察觉和诊断,但同时具备病毒传播能力。为研究无症状感染者对新型冠状病毒肺炎传播的影响,本文基于... 详细信息

新型冠状病毒肺炎(COVID-19,coronavirus disease 2019)的大流行对人类健康造成了巨大威胁。新型冠状病毒肺炎无症状感染者在早期不易被察觉和诊断,但同时具备病毒传播能力。为研究无症状感染者对新型冠状病毒肺炎传播的影响,本文基于之前建立的SCIRA微分方程模型与实际流行病学数据拟合并进行随机模拟。结果显示人群中无症状感染者的完全消除时间显著迟于确诊病例首次清零时间。严格的隔离防控手段可以降低人群间接触,有效阻断病毒传播。若严密防控措施不能在确诊病例全部治愈后予以保持,潜在的无症状感染者将可能诱导第二次疫情暴发。因此,即使确诊病例实现清零,仍需持续实施严格防控措施以遏制潜在的新型冠状病毒肺炎传播。

关键词：新型冠状病毒肺炎严格防控无症状感染者延迟治愈

Organic thin-film transistors and related devices in life and health monitoring

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Nano Research 2024年第2期17卷 426-444页

作者： Chenfang sun Tie Wang Tianjin Key Laboratory of Drug Targeting and Bioimaging Life and Health Intelligent Research InstituteTianjin University of TechnologyTianjin 300384China

The early determination of disease-related biomarkers can significantly improve the survival rate of patients.Thus,a series of explorations for new diagnosis technologies,such as optical and electrochemical methods,have been devoted to life and health monitoring.Organic thin-film transistor(OTFT),as a state-of-the-art nano-sensing technology,has attracted significant attention from construction to application owing to the merits of being label-free,low-cost,facial,and rapid detection with multi-parameter responses.Nevertheless,interference from non-specific adsorption is inevitable in complex biological samples such as body liquid and exhaled gas,so the reliability and accuracy of the biosensor need to be further improved while ensuring sensitivity,selectivity,and stability.Herein,we overviewed the composition,mechanism,and construction strategies of OTFTs for the practical determination of disease-related biomarkers in both body fluids and exhaled gas.The results show that the realization of bio-inspired applications will come true with the rapid development of high-effective OTFTs and related devices.

关键词： organic thin-film transistors biosensors biomarkers organic bioelectronics organic semiconductors healthcare

Pretreating and normalizing metabolomics data for statistical analysis

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Genes & Diseases 2024年第3期11卷 188-205页

作者： Jun sun Yinglin Xia Division of Gastroenterology and Hepatology Department of MedicineDepartment of Microbiology/ImmunologyUIC Cancer CenterUniversity of Illinois ChicagoJesse Brown VA Medical Center Chicago(537)ChicagoIL 60612USA Division of Gastroenterology and Hepatology Department of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA

Metabolomics as a research field and a set of techniques is to study the entire small molecules in biological samples.Metabolomics is emerging as a powerful tool generally for pre-cision medicine.Particularly,integration of microbiome and metabolome has revealed the mechanism and functionality of microbiome in human health and disease.However,metabo-lomics data are very complicated.Preprocessing/pretreating and normalizing procedures on metabolomics data are usually required before statistical analysis.In this review article,we comprehensively review various methods that are used to preprocess and pretreat metabolo-mics data,including MS-based data and NMR-based data preprocessing,dealing with zero and/or missing values and detecting outliers,data normalization,data centering and scaling,data transformation.We discuss the advantages and limitations of each method.The choice for a suitable preprocessing method is determined by the biological hypothesis,the characteristics of the data set,and the selected statistical data analysis method.We then provide the perspective of their applications in the microbiome and metabolome research.

关键词： Data centering and scaling Data normalization Data transformation Missing values MS-Baseddata preprocessing NMRData preprocessing Outliers Preprocessing/pretreatment

Fossil Equidae in the Linxia Basin with Biostratigraphic and Paleozoogeographic Significance

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Acta Geologica Sinica(English Edition) 2024年第1期98卷 1-9页

作者： sun Boyang Key Laboratory of Vertebrate Evolution and Human Origins of the Chinese Academy of Sciences Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China

The Linxia Basin is characterized by an abundance of Cenozoic sediments,that contain exceptionally rich fossil resources.Equids are abundant in the Linxia Basin,the fossil record of equids in this region including 16 species that represent 10 genera.In comparison to other classic late Cenozoic areas in China,the Linxia Basin stands out,because the fauna and chronological data accompanying Linxia equids render them remarkably useful for biostratigraphy.The anchitheriines in the region,such as Anchitherium and Sinohippus,represent early equids that appeared in the late stages of the middle and late Miocene,respectively.Among the equines,most species of Chinese hipparions have been identified in the Linxia Basin and some species of the genera Hipparion and Hippotherium have FAD records for China.Furthermore,Equus eisenmannae is one of the earliest known species of Equus in the Old World and is well-represented at the Longdan locality.Some species with precise geohistorical distributions can serve as standards for high-resolution chronological units within this framework.Located at the eastern margin of the Tibetan Plateau and subject to considerable uplift,the Linxia Basin has served as a biogeographic transition area for equids throughout the late Cenozoic.

关键词： Equidae Cenozoic biostratigraphy paleozoogeography Linxia Basin

NADPH oxidase 4(NOX4)as a biomarker and therapeutic target in neurodegenerative diseases

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Neural Regeneration Research 2024年第9期19卷 1961-1966页

作者： Napissara Boonpraman sun Shin Yi BK21 four Program Department of Medical SciencesSoonchunhyang UniversityAsanSouth Korea Department of Biomedical Laboratory Science Soonchunhyang UniversityAsanSouth Korea iConnectome Co.Ltd.CheonanSouth Korea

Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.

关键词： Alzheimer’s disease astrocytes mitochondrial dysfunction myeloperoxidase NADPH oxidase 4 NADPH oxidase 4 inhibitors neurodegenerative diseases osteopontin Parkinson’s disease reactive oxygen species